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Choy KW, Wijeratne N, Chiang C, Don-Wauchope A. Copeptin as a surrogate marker for arginine vasopressin: analytical insights, current utility, and emerging applications. Crit Rev Clin Lab Sci 2025; 62:24-44. [PMID: 39086073 DOI: 10.1080/10408363.2024.2383899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/01/2024] [Accepted: 07/19/2024] [Indexed: 08/02/2024]
Abstract
Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable in vitro. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimated glomerular filtration rate and a greater risk of new-onset chronic kidney disease. Furthermore, copeptin is associated with disease severity in patients with autosomal dominant polycystic kidney disease. Copeptin predicts the development of coronary artery disease and cardiovascular mortality in the older population. Moreover, the predictive value of copeptin was found to be comparable with that of N-terminal pro-brain natriuretic peptide for all-cause mortality in patients with heart failure. Whether the measurement of copeptin in these conditions alters clinical management remains to be demonstrated in future studies.
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Affiliation(s)
- Kay Weng Choy
- Department of Pathology, Northern Health, Epping, Australia
| | - Nilika Wijeratne
- Eastern Health Pathology, Eastern Health, Box Hill, Australia
- Department of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia
| | - Cherie Chiang
- Department of Medicine, The University of Melbourne, Melbourne, Australia
- Department of Internal Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
- Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Australia
| | - Andrew Don-Wauchope
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
- Laverty Pathology, North Ryde, Australia
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Vasile AI, Tiu C, Badiu C. Copeptin as biomarker for acute ischemic stroke prognosis and revascularization treatment efficacy. Front Neurol 2024; 15:1447355. [PMID: 39777314 PMCID: PMC11705377 DOI: 10.3389/fneur.2024.1447355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 11/28/2024] [Indexed: 01/11/2025] Open
Abstract
Introduction Pro-arginine vasopressin consists of three peptides: arginine-vasopressin, neurophysin II, and copeptin. AVP is released by the neurohypophysis in response to increased plasma osmolality, decreased blood volume and stress. Copeptin has the advantage of being stable ex vivo and easy to measure. New data show the importance of copeptin in ischemic stroke and its complications. Methods We present a literature review that highlights the importance of copeptin as a biological marker for stroke. We searched the Pubmed and Scopus databases for papers with the following keywords: "stroke AND copeptin." PRISMA criteria were used. Results We identified 332 papers that met the criteria. We excluded analyzed reviews, systematic reviews and meta-analyses. 31 articles resulted. The number of patients included in the analyzed studies varied between 18 and 4,302. Copeptin is a marker that associated with clinical stroke severity, infarct volume, short-term and long-term functionality and mortality and adds prognostic value to the previously used scales. It may reflect the effectiveness of revascularization therapy. Copeptin is a biomarker that can help predict post-stroke complications such as: cerebral edema and hemorrhagic transformation. Discussion Copeptin is a novel and promising biomarker for evaluating cerebrovascular diseases. Because it is considered a non-specific biomarker, it is not yet used routinely and it cannot replace the clinical examination. However, combined with other clinical or paraclinical parameters, it can increase the accuracy of the diagnosis.
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Affiliation(s)
- Antonia Ioana Vasile
- Neurology Department, University Emergency Hospital of Bucharest, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Cristina Tiu
- Neurology Department, University Emergency Hospital of Bucharest, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Corin Badiu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Endocrinology IV, C.I. Parhon National Institute of Endocrinology, Bucharest, Romania
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Szczepanska-Sadowska E, Cudnoch-Jędrzejewska A, Żera T. Molecular Interaction Between Vasopressin and Insulin in Regulation of Metabolism: Impact on Cardiovascular and Metabolic Diseases. Int J Mol Sci 2024; 25:13307. [PMID: 39769071 PMCID: PMC11678547 DOI: 10.3390/ijms252413307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/05/2024] [Accepted: 12/09/2024] [Indexed: 01/04/2025] Open
Abstract
Numerous compounds involved in the regulation of the cardiovascular system are also engaged in the control of metabolism. This review gives a survey of literature showing that arginine vasopressin (AVP), which is an effective cardiovascular peptide, exerts several direct and indirect metabolic effects and may play the role of the link adjusting blood supply to metabolism of tissues. Secretion of AVP and activation of AVP receptors are regulated by changes in blood pressure and body fluid osmolality, hypoxia, hyperglycemia, oxidative stress, inflammation, and several metabolic hormones; moreover, AVP turnover is regulated by insulin. Acting on V1a receptors in the liver, AVP stimulates glycogenolysis, reduces synthesis of glycogen, and promotes fatty acid synthesis and acetyl CoA carboxylase activity. Stimulating V1b receptors in the pancreatic islands, AVP promotes release of insulin and glucagon-like peptide-1 (GLP-1) and potentiates stimulatory effects of glucose and ACTH on secretion of insulin. Simultaneously, insulin increases AVP secretion by neurons of the paraventricular nucleus and the supraoptic nucleus. There is strong evidence that secretion of AVP and its metabolic effectiveness are significantly altered in metabolic and cardiovascular diseases. Both experimental and clinical data indicate that inappropriate interactions of AVP and insulin play an important role in the development of insulin resistance in obesity and diabetes mellitus.
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Affiliation(s)
- Ewa Szczepanska-Sadowska
- Department of Experimental and Clinical Physiology, Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland
| | | | - Tymoteusz Żera
- Department of Experimental and Clinical Physiology, Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland
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Le Page AK, Johnson EC, Greenberg JH. Is mild dehydration a risk for progression of childhood chronic kidney disease? Pediatr Nephrol 2024; 39:3177-3191. [PMID: 38632124 PMCID: PMC11413076 DOI: 10.1007/s00467-024-06332-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 04/19/2024]
Abstract
Children with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.
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Affiliation(s)
- Amelia K Le Page
- Department of Nephrology, Monash Children's Hospital, Clayton, VIC, Australia.
- Department of Pediatrics, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
| | - Evan C Johnson
- Division of Kinesiology & Health, College of Health Sciences, University of Wyoming, Laramie, WY, USA
| | - Jason H Greenberg
- Section of Nephrology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
- Department of Internal Medicine, Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA
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Matsuda T, Osaki Y, Maruo K, Matsuda E, Suzuki Y, Suzuki H, Mathis BJ, Shimano H, Mizutani M. Variability of urinary albumin to creatinine ratio and eGFR are independently associated with eGFR slope in Japanese with type 2 diabetes: a three-year, single-center, retrospective cohort study. BMC Nephrol 2024; 25:264. [PMID: 39152372 PMCID: PMC11330002 DOI: 10.1186/s12882-024-03699-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/07/2024] [Indexed: 08/19/2024] Open
Abstract
BACKGROUND To evaluate the seasonal variability of urinary albumin to creatinine ratio (UACR) and eGFR and these effects on three-year eGFR slope in persons with type 2 diabetes (T2D). METHODS A total of 1135 persons with T2D were analyzed in this single-center, retrospective cohort study in Japan. The standard deviation (SD) of UACR (SD [UACR]) and SD of eGFR (SD [eGFR]) were calculated for each person's 10-point data during the three years, and a multiple linear regression analysis was performed to evaluate associations with eGFR slope. A sensitivity analysis was performed in a group with no medication changes (n = 801). RESULTS UACR exhibited seasonal variability, being higher in winter and lower in spring, early summer, and autumn especially in the UACR ≥ 30 mg/g subgroup, while eGFR showed no seasonal variability. The eGFR slope was significantly associated with SD (eGFR) (regression coefficient -0.170 [95% CI -0.189--0.151]) and SD (UACR) (0.000 [-0.001-0.000]). SGLT-2 inhibitors, baseline eGFR, and baseline systolic blood pressure (SBP) were also significantly associated. These associated factors, except baseline SBP, were still significant in the sensitivity analysis. CONCLUSIONS The UACR showed clear seasonal variability. Moreover, SD (UACR) and SD (eGFR) were independently associated with a three-year eGFR slope in persons with T2D. TRIAL REGISTRATION This study was not registered for clinical trial registration because it was a retrospective observational study.
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Affiliation(s)
- Takaaki Matsuda
- Department of Internal Medicine, Kozawa Eye Hospital and Diabetes Center, 246-6 Yoshizawa-cho, Mito, Ibaraki, 310-0845, Japan.
- Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
- Tsukuba Clinical Research and Development Organization (T-CReDO), University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Yoshinori Osaki
- Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kazushi Maruo
- Tsukuba Clinical Research and Development Organization (T-CReDO), University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Erika Matsuda
- Department of Internal Medicine, Kozawa Eye Hospital and Diabetes Center, 246-6 Yoshizawa-cho, Mito, Ibaraki, 310-0845, Japan
- Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yasuhiro Suzuki
- Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
- Institute of Systems and Information Engineering, University of Tsukuba, Tsukuba, Ibaraki, 305-8573, Japan
| | - Hiroaki Suzuki
- Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Food and Health Sciences, Faculty of Human Life Sciences, Jissen Women's University, Hino, Tokyo, 191-8510, Japan
| | - Bryan J Mathis
- Department of Cardiovascular Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hitoshi Shimano
- Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Masakazu Mizutani
- Department of Internal Medicine, Kozawa Eye Hospital and Diabetes Center, 246-6 Yoshizawa-cho, Mito, Ibaraki, 310-0845, Japan
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Paz-Graniel I, Valle-Hita C, Babio N, Serra-Majem L, Vioque J, Zomeño MD, Corella D, Pintó X, Cano-Ibáñez N, Tur JA, Cuadrado-Soto E, Martínez JA, Díaz-López A, Torres-Collado L, Goday A, Fernández-Carrión R, Nissenshon M, Riera-Mestre A, Garrido-Garrido E, Bouzas C, Abete I, Daimiel L, Cornejo-Pareja I, Vázquez-Ruiz Z, Khoury N, Pérez-Vega KA, Salas-Salvadó J. Long-term association between water intake and kidney function in a population at high cardiovascular risk. J Nutr Health Aging 2024; 28:100327. [PMID: 39137622 DOI: 10.1016/j.jnha.2024.100327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/23/2024] [Accepted: 07/26/2024] [Indexed: 08/15/2024]
Abstract
OBJECTIVES The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR). METHODS Three-year prospective analysis conducted in 1986 older adults (aged 55-75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m2) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up. RESULTS Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: β: 1.4 ml/min/1.73 m2; 95%CI: 0.5-2.3, β: 1.0; 95%CI: 0.1-2.0, respectively). CONCLUSIONS Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk. TRIAL REGISTRATION ISRCTN89898870. Retrospectively registered on 24 July 2014.
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Affiliation(s)
- Indira Paz-Graniel
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnología, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - Cristina Valle-Hita
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnología, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - Nancy Babio
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnología, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - Lluís Serra-Majem
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria & Centro Hospitalario Universitario Insular Materno Infantil (CHUIMI), Canarian Health Service, Las Palmas de Gran Canaria, Spain
| | - Jesus Vioque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - María Dolores Zomeño
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Cardiovascular Risk and Nutrition, Hospital del Mar Medical Research Institute, Barcelona, Spain; School of Health Sciences, Blanquerna-Ramon Llull University, Barcelona, Spain
| | - Dolores Corella
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Departament of Preventive Medicine and Public Health, School of Medicine, Valencia, Spain
| | - Xavier Pintó
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Internal Medicine Department. Hospital Universitari Bellvitge, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Clinical Sciences Department, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Naomi Cano-Ibáñez
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria (ibs. GRANADA), Complejo Hospitales Universitarios de Granada/Universidad de Granada, 18071, Granada, Spain
| | - Josep A Tur
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands, Palma de Mallorca, Spain; Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain
| | - Esther Cuadrado-Soto
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM+CSIC, Madrid, Spain; Grupo de Investigación VALORNUT-UCM, Departamento de Nutrición y Ciencia de los Alimentos, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - J A Martínez
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain; Precision Nutrition and Cardiometabolic Health Program, IEA Food, CEI UAM+CSIC, Madrid, Spain; Departament of Medicine and Endocrinology, University of Valladolid, Spain
| | - Andrés Díaz-López
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain; Nutrition and Mental Health (NUTRISAM) Research Group, Nutrition and Public Health Unit, Universitat Rovira I Virgili, Reus 43204, Spain
| | - Laura Torres-Collado
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - Albert Goday
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; IMIM, Endocrinology and Diabetes Unit, Hospital del Mar, Barcelona, Spain; Departament de Medicina, Universitat Autónoma de Barcelona, Spain
| | - Rebeca Fernández-Carrión
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Departament of Preventive Medicine and Public Health, School of Medicine, Valencia, Spain
| | - Mariela Nissenshon
- Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria & Centro Hospitalario Universitario Insular Materno Infantil (CHUIMI), Canarian Health Service, Las Palmas de Gran Canaria, Spain
| | - Antoni Riera-Mestre
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Internal Medicine Department. Hospital Universitari Bellvitge, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Clinical Sciences Department, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
| | - Eva Garrido-Garrido
- Primary Care Center Zaidín-Center, Andalusian Health Service, Granada, Spain
| | - Cristina Bouzas
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands, Palma de Mallorca, Spain; Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain
| | - Itziar Abete
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Lidia Daimiel
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM+CSIC, Madrid, Spain; Departamento de Ciencias Farmacéuticas y de la Salud, Faculty de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Spain
| | - Isabel Cornejo-Pareja
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Virgen de la Victoria Hospital, Department of Endocrinology, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Málaga, 29010 Málaga, Spain
| | - Zenaida Vázquez-Ruiz
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine and Public Health, Instituto de Investigación Sanitaria de Navarra (IdiSNA), University of Navarra, 31008 Pamplona, Spain
| | - Nadine Khoury
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnología, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - Karla Alejandra Pérez-Vega
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Cardiovascular Risk and Nutrition, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Jordi Salas-Salvadó
- Consorcio Centro de Investigación Biomédica en Red, M.P. Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnología, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
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Cole NI, Swift PA, Suckling RJ, He FJ, Gallagher H, van Vlymen J, Byford R, de Lusignan S. The Relationship between Serum Sodium Concentration and Albuminuria: A Retrospective Cohort Study. Nephron Clin Pract 2024; 148:701-711. [PMID: 39038444 DOI: 10.1159/000538819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/04/2024] [Indexed: 07/24/2024] Open
Abstract
BACKGROUND Lowering dietary salt intake reduces albuminuria, an early marker of renal damage and a sensitive predictor of adverse cardiovascular outcomes. The mechanisms underlying this effect are uncertain but small changes in serum sodium concentration may be important: this retrospective cohort study investigated the hypothesis that higher serum sodium concentration is a risk factor for albuminuria (defined as a urine albumin:creatinine ratio [UACR], ≥3 mg/mmol). METHODS Primary care data from the Royal College of General Practitioners Research and Surveillance Centre were used to identify 47,294 individuals with a UACR result available between April 2010 and March 2015, and no known albuminuria prior to this. Exclusion criteria were missing or abnormal serum sodium concentration at baseline (<135 or >146 mmol/L); age <18 years; diabetes mellitus; decompensated liver disease; heart failure; and stage 5 chronic kidney disease. RESULTS After adjustment for known risk factors, there was a significant "U-shaped" relationship between serum sodium concentration and albuminuria. The lowest risk was associated with a serum sodium of 138-140 mmol/L. In comparison, the risk of albuminuria was 18% higher with a serum sodium of 135-137 mmol/L and 19% higher with a serum sodium of 144-146 mmol/L. There was no association between serum sodium concentration and blood pressure. CONCLUSION The finding of a positive association between higher serum sodium concentration and albuminuria is in support of the hypothesis, but the inverse relationship between serum sodium concentration and albuminuria at lower concentrations warrants further explanation.
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Affiliation(s)
- Nicholas I Cole
- Renal Department, Epsom and St Helier University Hospitals NHS Trust, Epsom, UK
| | - Pauline A Swift
- Renal Department, Epsom and St Helier University Hospitals NHS Trust, Epsom, UK
| | - Rebecca J Suckling
- Renal Department, Epsom and St Helier University Hospitals NHS Trust, Epsom, UK
| | - Feng J He
- Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK
| | - Hugh Gallagher
- Renal Department, Epsom and St Helier University Hospitals NHS Trust, Epsom, UK
| | - Jeremy van Vlymen
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Rachel Byford
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Simon de Lusignan
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
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Dawman L, Rawat A, Meena J, Tiewsoh K. Copeptin as a potential biomarker of chronic kidney disease to predict the disease progression in children with chronic kidney disease. J Family Med Prim Care 2024; 13:2044-2048. [PMID: 38948594 PMCID: PMC11213435 DOI: 10.4103/jfmpc.jfmpc_1707_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 07/02/2024] Open
Abstract
Background Biomarkers to predict the onset and progression of chronic kidney disease (CKD) in children are lacking, and no such definite biomarkers have been implicated in the diagnosis of CKD. We conducted this study to evaluate copeptin as a CKD marker and predict the disease progression by estimating the copeptin levels at baseline and 12 months follow-up in children with CKD stage 2 and above. Materials and Methods This prospective single-centre cohort study was conducted in children under 14 years with CKD stages 2-4. Blood and urine samples were collected at enrolment and 1-year follow-up for routine investigations and serum copeptin, cystatin C and urinary neutrophil gelatinase-associated lipocalcin (uNGAL) estimation. Results A total of 110 children (60 cases and 50 controls) were enrolled in the study. The mean estimated glomerular filtration rate (eGFR) of cases was 58.3 ± 18.7 ml/min/1.73 m2. Among the cases, there was a significant rise in the serum copeptin levels from baseline 483.08 ± 319.2 pg/ml to follow-up at 1 year, that is, 1046.82 ± 823.53 pg/ml (P < 0.0001). A significant difference was noted in the baseline values of serum cystatin C, that is, 1512.98 ± 643.77 ng/ml and 719.68 ± 106.96 ng/ml (P < 0.0001), and uNGAL, that is, 13.53 ± 11.72 and 1.76 ± 2.37 ng/ml (P < 0.0001) between the cases and controls. There was no significant correlation (correlation coefficient = 0.10) between change in eGFR and copeptin levels during 12 months of follow-up. Conclusion No significant correlation was found between the change in eGFR and copeptin levels during 12 months of follow-up. This can be due to the slow deterioration of renal functions, as most of the cases had underlying congenital anomalies of the kidney and urinary tract (CAKUT), which is known to have a slow progression of CKD and a small sample size.
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Affiliation(s)
- Lesa Dawman
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Amit Rawat
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Jitendra Meena
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Karalanglin Tiewsoh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Jaques DA, Dufey Teso A, Wuerzner G, Martinez De Tejada B, Santagata M, Othenin Girard V, Le Tinier B, Pechere Bertschi A, Ponte B. Association of serum copeptin and urinary uromodulin with kidney function, blood pressure and albuminuria at 6 weeks post-partum in pre-eclampsia. Front Cardiovasc Med 2024; 11:1310300. [PMID: 38500759 PMCID: PMC10945001 DOI: 10.3389/fcvm.2024.1310300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 02/14/2024] [Indexed: 03/20/2024] Open
Abstract
Background Preeclampsia (PE) is associated with subsequent higher risk of cardiovascular and kidney disease. Serum copeptin, as a proxy for vasopressin, and urinary uromodulin, were associated with PE physiopathology and kidney functional mass respectively. We describe concentrations of these proteins in the post-partum period and characterize their association with persistent hypertension (HTN) or albuminuria. Methods Patients with PE and healthy controls with uncomplicated pregnancy were prospectively included at two teaching hospitals in Switzerland. Clinical parameters along with serum copeptin and urinary uromodulin were measured at 6 weeks post-partum. PE patients were further characterized based on presence of HTN (defined as either systolic BP (SBP) ≥140 mmHg or diastolic (BP) ≥90 mmHg) or albuminuria [defined as urinary albumin to creatinine ratio (ACR) ≥3 mg/mmol]. Results We included 226 patients with 35 controls, 120 (62.8%) PE with persistent HTN/albuminuria and 71 (37.1%) PE without persistent HTN/albuminuria. Median serum copeptin concentration was 4.27 (2.9-6.2) pmol/L without differences between study groups (p > 0.05). Higher copeptin levels were associated with higher SBP in controls (p = 0.039), but not in PE (p > 0.05). Median urinary uromodulin concentration was 17.5 (7.8-28.7) mg/g with lower levels in PE patients as compared to healthy controls (p < 0.001), but comparable levels between PE patients with or without HTN/albuminuria (p > 0.05). Higher uromodulin levels were associated with lower albuminuria in PE as well as control patients (p = 0.040). Conclusion Serum copeptin levels at 6 weeks post-partum are similar between PE patients and healthy controls and cannot distinguish between PE with or without residual kidney damage. This would argue against a significant pathophysiological role of the vasopressin pathway in mediating organ damage in the post-partum period. On the opposite, post-partum urinary uromodulin levels are markedly lower in PE patients as compared to healthy controls, potentially reflecting an increased susceptibility to vascular and kidney damage that could associate with adverse long-term cardiovascular and kidney outcomes.
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Affiliation(s)
- David A. Jaques
- Service of Nephrology and Hypertension, Geneva University Hospitals, Geneva, Switzerland
| | - Anne Dufey Teso
- Service of Nephrology and Hypertension, Geneva University Hospitals, Geneva, Switzerland
| | - Grégoire Wuerzner
- Service of Nephrology and Hypertension, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Begona Martinez De Tejada
- Division of Obstetrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland
- Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Marika Santagata
- Division of Obstetrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland
| | - Véronique Othenin Girard
- Division of Obstetrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland
| | - Bénédicte Le Tinier
- Division of Obstetrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland
| | | | - Belen Ponte
- Service of Nephrology and Hypertension, Geneva University Hospitals, Geneva, Switzerland
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10
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Маркова ТН, Косова ЕВ, Мищенко НК. [Pituitary disorders in patients with end-stage chronic renal failure]. PROBLEMY ENDOKRINOLOGII 2024; 69:37-46. [PMID: 38311993 PMCID: PMC10848192 DOI: 10.14341/probl13212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 04/07/2023] [Accepted: 06/06/2023] [Indexed: 02/06/2024]
Abstract
Disorders in the kidneys lead to disturbance of homeostasis. As the glomerular filtration rate decreases, the metabolism of numerous biologically active substances, including pituitary hormones, decreases. The article presents an overview of pituitary dysfunction in patients with chronic kidney disease (CKD) and discusses the possible reasons of the pathogenetic mechanisms. Particular focus is being given to the assessment of changes in the concentration of pituitary hormones in patients with end-stage chronic kidney disease (CKD) and discusses the pathogenetic mechanisms of their formation. Particular attention is paid to the assessment of changes in the concentration of pituitary hormones in patients receiving renal replacement therapy (RRT). CKD leads to an increase in the level of prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Concentrations of growth hormone (GH), isulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and vasopressin may remain within normal values or increase in this group of patients. RRT does not reduce the levels of prolactin, LH, FSH, while the concentration of growth hormone, IGF-1, TSH tends to normalize. The content of ACTH and vasopressin may remain unchanged or decrease. Kidney transplantation in most cases corrects hormonal disorders. Correction of hormonal changes can improve the clinical outcome and quality of life of patients with end stage CKD.
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Affiliation(s)
- Т. Н. Маркова
- Московский государственный медико-стоматологический университет им. А.И. Евдокимова; Городская клиническая больница № 52 ДЗМ
| | - Е. В. Косова
- Московский государственный медико-стоматологический университет им. А.И. Евдокимова
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11
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Michon-Colin A, Metzger M, Bankir L, Gauci C, Brunel M, Baron S, Prot-Bertoye C, Stengel B, Thervet E, Haymann JP, Boffa JJ, Vrtovsnik F, Flamant M, Houillier P, Prie D, Courbebaisse M. Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease. Clin Kidney J 2023; 16:2472-2481. [PMID: 38046034 PMCID: PMC10689138 DOI: 10.1093/ckj/sfad149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Indexed: 12/05/2023] Open
Abstract
Background Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. Methods We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. Results A total of 329 CKD patients (243 men, mean age 60.3 ± 14.6 years) were included. Among them, 301 with an mGFR >15 ml/min/1.73 m2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61 years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Conclusion Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD.
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Affiliation(s)
- Arthur Michon-Colin
- Université Paris Cité, Paris, France
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Paris, France
- Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, France
| | - Marie Metzger
- INSERM UMRS 1018, Equipe d'Epidémiologie Clinique, CESP, Université Paris-Saclay, Villejuif, France
| | - Lise Bankir
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France
- CNRS, ERL 8228, Laboratory of Kidney Physiology and Tubulopathies, Paris, France
| | - Cédric Gauci
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- INSERM UMRS 1018, Equipe d'Epidémiologie Clinique, CESP, Université Paris-Saclay, Villejuif, France
| | - Mélanie Brunel
- Université Paris Cité, Paris, France
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Paris, France
- Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, France
| | - Stéphanie Baron
- Université Paris Cité, Paris, France
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France
- Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Paris, France
- Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, France
| | - Caroline Prot-Bertoye
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France
- CNRS, ERL 8228, Laboratory of Kidney Physiology and Tubulopathies, Paris, France
- Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Paris, France
- Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, France
| | - Bénédicte Stengel
- INSERM UMRS 1018, Equipe d'Epidémiologie Clinique, CESP, Université Paris-Saclay, Villejuif, France
| | - Eric Thervet
- Université Paris Cité, Paris, France
- Néphrologie et Hémodialyse, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Jean-Philippe Haymann
- Explorations Fonctionnelles Multidisciplinaires, Sorbonne Université Paris, France
- Explorations Fonctionnelles Multidisciplinaires, Hôpital Tenon, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Jean-Jacques Boffa
- Explorations Fonctionnelles Multidisciplinaires, Sorbonne Université Paris, France
- Néphrologie et Dialyse, Hôpital Tenon, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - François Vrtovsnik
- Université Paris Cité, Paris, France
- Néphrologie, Hôpital Bichat, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Martin Flamant
- Université Paris Cité, Paris, France
- Explorations Fonctionnelles Multidisciplinaires, Hôpital Bichat, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Pascal Houillier
- Université Paris Cité, Paris, France
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France
- Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Paris, France
- Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, France
| | - Dominique Prie
- Université Paris Cité, Paris, France
- INSERM U1151, Institut Necker Enfants Malades, Paris, France
- Département de Physiologie, Hôpital Necker, Assistance Publique – Hôpitaux de Paris, Paris, France
| | - Marie Courbebaisse
- Université Paris Cité, Paris, France
- Explorations Fonctionnelles Rénales – Physiologie, Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, Paris, France
- INSERM U1151, Institut Necker Enfants Malades, Paris, France
- Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Paris, France
- Centre de Référence des Maladies Rares du Calcium et du Phosphate, Paris, France
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Sorić Hosman I, Cvitković Roić A, Fištrek Prlić M, Vuković Brinar I, Lamot L. Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers. Front Pediatr 2023; 11:1274435. [PMID: 38027263 PMCID: PMC10667601 DOI: 10.3389/fped.2023.1274435] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023] Open
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is one of the leading causes of end-stage renal disease. In spite of the recent tremendous progress in the understanding of ADPKD pathogenesis, the molecular mechanisms of the disease remain incompletely understood. Considering emerging new targeted therapies for ADPKD, it has become crucial to disclose easily measurable and widely available biomarkers for identifying patients with future rapid disease progression. This review encompasses all the research with a shared goal of identifying promising serum or urine biomarkers for predicting ADPKD progression or response to therapy. The rate of the ADPKD progress varies significantly between patients. The phenotypic variability is only partly explained by the underlying genetic lesion diversity. Considering significant decline in kidney function in ADPKD is not usually evident until at least 50% of the parenchyma has been destroyed, conventional kidney function measures, such as glomerular filtration rate (GFR), are not suitable for monitoring disease progression in ADPKD, particularly in its early stages. Since polycystic kidney enlargement usually precedes the decline in GFR, height-adjusted total kidney volume (ht-TKV) has been accepted as an early biomarker for assessing disease severity in ADPKD patients. However, since measuring ht-TKV is time-consuming and observer-dependent, the identification of a sensitive and quickly measurable biomarker is of a great interest for everyday clinical practice. Throughout the last decade, due to development of proteomic and metabolomic techniques and the enlightenment of multiple molecular pathways involved in the ADPKD pathogenesis, a number of urine and serum protein biomarkers have been investigated in ADPKD patients, some of which seem worth of further exploring. These include copeptin, angiotensinogen, monocyte chemoattractant protein 1, kidney injury molecule-1 and urine-to-plasma urea ratio among many others. The aim of the current review is to provide an overview of all of the published evidence on potentially clinically valuable serum and urine biomarkers that could be used for predicting disease progression or response to therapy in patients with ADPKD. Hopefully, this review will encourage future longitudinal prospective clinical studies evaluating proposed biomarkers as prognostic tools to improve management and outcome of ADPKD patients in everyday clinical practice.
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Affiliation(s)
- Iva Sorić Hosman
- Department of Pediatrics, General Hospital Zadar, Zadar, Croatia
| | - Andrea Cvitković Roić
- Department of Nephrology and Urology, Clinic for Pediatric Medicine Helena, Zagreb, Croatia
- Department of Pediatrics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Department of Pediatrics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Margareta Fištrek Prlić
- Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Ivana Vuković Brinar
- Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Lovro Lamot
- Division of Nephrology, Dialysis and Transplantation, Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia
- Department of Pediatrics, School of Medicine, University of Zagreb, Zagreb, Croatia
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13
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Franzén A, Pikkemaat M, Melander O, Bennet L, Enhörning S. The association of copeptin with metabolic risk markers is modified by region of origin. Sci Rep 2023; 13:19651. [PMID: 37949932 PMCID: PMC10638355 DOI: 10.1038/s41598-023-46908-0] [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: 01/24/2023] [Accepted: 11/07/2023] [Indexed: 11/12/2023] Open
Abstract
Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the MEDIM cohort we investigated differences in copeptin levels between Iraqi and Swedish born individuals and if the association between copeptin and cardiometabolic risk markers differed by region of origin. We included 1109 Iraqi and 613 Swedish born participants (58% men, mean age 47 years). The Swedish participants had a higher concentration of copeptin compared to the Iraqi born group after age and sex adjustment (p < 0.001). This difference existed only among male individuals with the highest copeptin concentrations, i.e. belonging to copeptin quartile 4 (median (25th; 75th percentile) 20.07 (15.27;33.28) pmol/L for the Swedish born versus 15.57 (13.91;19.00) pmol/L for the Iraqi born, p < 0.001). We found a significant interaction between copeptin (continuous ln-transformed) and being born in Iraq regarding the association with plasma triglycerides (Pinteraction = 0.006). The association between copeptin and BMI was stronger amongst the Iraqi born individuals compared to the Swedish born. Together, this could indicate that copeptin is a more potent marker of metabolic disease among individuals born in Iraq compared to Sweden.
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Affiliation(s)
- Anna Franzén
- Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center 91:12, Jan Waldenströms gata 35, 21428, Malmö, Sweden.
| | - Miriam Pikkemaat
- Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center 91:12, Jan Waldenströms gata 35, 21428, Malmö, Sweden
| | - Olle Melander
- Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center 91:12, Jan Waldenströms gata 35, 21428, Malmö, Sweden
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
| | - Louise Bennet
- Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center 91:12, Jan Waldenströms gata 35, 21428, Malmö, Sweden
- Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden
| | - Sofia Enhörning
- Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center 91:12, Jan Waldenströms gata 35, 21428, Malmö, Sweden
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
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Arjune S, Oehm S, Todorova P, Gansevoort RT, Bakker SJL, Erger F, Benzing T, Burst V, Grundmann F, Antczak P, Müller RU. Copeptin in autosomal dominant polycystic kidney disease: real-world experiences from a large prospective cohort study. Clin Kidney J 2023; 16:2194-2204. [PMID: 37915893 PMCID: PMC10616446 DOI: 10.1093/ckj/sfad118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Indexed: 11/03/2023] Open
Abstract
Background The identification of new biomarkers in autosomal-dominant polycystic kidney disease (ADPKD) is crucial to improve and simplify prognostic assessment as a basis for patient selection for targeted therapies. Post hoc analyses of the TEMPO 3:4 study indicated that copeptin could be one of those biomarkers. Methods Copeptin was tested in serum samples from patients of the AD(H)PKD study. Serum copeptin levels were measured using a time-resolved amplified cryptate emission (TRACE)-based assay. In total, we collected 711 values from 389 patients without tolvaptan treatment and a total of 243 values (of which 64 were pre-tolvaptan) from 94 patients on tolvaptan. These were associated with rapid progression and disease-causing gene variants and their predictive capacity tested and compared with the Mayo Classification. Results As expected, copeptin levels showed a significant negative correlation with estimated glomerular filtration rate (eGFR). Measurements on tolvaptan showed significantly higher copeptin levels (9.871 pmol/L vs 23.90 pmol/L at 90/30 mg; P < .0001) in all chronic kidney disease stages. Linear regression models (n = 133) show that copeptin is an independent predictor of eGFR slope. A clinical model (including eGFR, age, gender, copeptin) was nearly as good (R2 = 0.1196) as our optimal model (including height-adjusted total kidney volume, eGFR, copeptin, R2 = 0.1256). Adding copeptin to the Mayo model improved future eGFR estimation. Conclusion Copeptin levels are associated with kidney function and independently explained future eGFR slopes. As expected, treatment with tolvaptan strongly increases copeptin levels.
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Affiliation(s)
- Sita Arjune
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Simon Oehm
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Polina Todorova
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Ron T Gansevoort
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Florian Erger
- Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Institute of Human Genetics, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Thomas Benzing
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Volker Burst
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Emergency Department, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany
| | - Franziska Grundmann
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
| | - Philipp Antczak
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Roman-Ulrich Müller
- Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
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15
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Nakae A, Ozaki E, Kuriyama N, Tomida S, Koyama T. Copeptin is associated with microalbuminuria and renal function in the general Japanese population. Endocr J 2023; 70:797-804. [PMID: 37286517 DOI: 10.1507/endocrj.ej23-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/09/2023] Open
Abstract
An association between copeptin (precursor molecule of arginine vasopressin) and markers for renal function has been reported, but data on the Japanese population has been limited. In this study, we investigated whether elevated copeptin levels are associated with microalbuminuria and renal dysfunction in the general Japanese population. A total of 1,262 participants (842 female and 420 male) were enrolled. Multiple regression analysis was performed to assess the association of copeptin levels (logarithm) with estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR) after adjusting for age, BMI, and lifestyle variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression methods in which chronic kidney disease (CKD) was the dependent variable. The copeptin levels differed significantly with sex, but were not found to be related to age or the span of time from preceding meal to blood sampling. In female participants, copeptin level was negatively correlated with eGFR (beta = -0.100, p-value = 0.006) and positively correlated with UACR (beta = 0.099, p-value = 0.003). In male participants, a negative correlation (beta = -0.140, p-value = 0.008) was observed for eGFR. In both females and males, those with high copeptin levels had more than double the ORs of CKD (OR = 2.1-2.9) adjusted for CKD-related factors. The present study found elevated copeptin levels to be associated with renal function loss in the Japanese population and microalbuminuria in female. Moreover, it was evident that high copeptin levels are associated with CKD. These results suggest that copeptin could be considered a marker of renal function.
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Affiliation(s)
- Aya Nakae
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan
| | - Etsuko Ozaki
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan
| | - Nagato Kuriyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan
- Shizuoka Graduate University of Public Health, Shizuoka 420-0881, Japan
| | - Satomi Tomida
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan
- Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan
| | - Teruhide Koyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan
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16
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Broadening horizons in mechanisms, management, and treatment of diabetic kidney disease. Pharmacol Res 2023; 190:106710. [PMID: 36871895 DOI: 10.1016/j.phrs.2023.106710] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023]
Abstract
Diabetic kidney disease (DKD) is the first cause of end-stage kidney disease in patients with diabetes and its prevalence is increasing worldwide. It encompasses histological alterations that mainly affect the glomerular filtration unit, which include thickening of the basement membrane, mesangial cell proliferation, endothelial alteration, and podocyte injury. These morphological abnormalities further result in a persistent increase of urinary albumin-to-creatinine ratio and in a reduction of the estimated glomerular filtration rate. Several molecular and cellular mechanisms have been recognized, up to date, as major players in mediating such clinical and histological features and many more are being under investigation. This review summarizes the most recent advances in understanding cell death mechanisms, intracellular signaling pathways and molecular effectors that play a role in the onset and progression of diabetic kidney damage. Some of those molecular and cellular mechanisms have been already successfully targeted in preclinical models of DKD and, in some cases, strategies have been tested in clinical trials. Finally, this report sheds light on the relevance of novel pathways that may become therapeutic targets for future applications in DKD.
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17
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Iglesias P, Silvestre RA, Fernández-Reyes MJ, Díez JJ. The role of copeptin in kidney disease. Endocrine 2023; 79:420-429. [PMID: 36242751 DOI: 10.1007/s12020-022-03219-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/30/2022] [Indexed: 11/25/2022]
Abstract
Copeptin is a 39-amino acid glycopeptide that is secreted equimolecularly with arginine-vasopressin (AVP) from the prepro-hormone AVP in the posterior pituitary. While AVP is a very unstable molecule and is accompanied by significant technical troubles in its quantification, copeptin is a stable and easily quantifiable molecule. For this reason, circulating copeptin is currently used as a surrogate for AVP in different pathological conditions, including renal diseases. In recent years it has been shown that copeptin is associated with an increased risk of developing chronic kidney disease in the general population. In addition, copeptin has also been associated with multiple renal diseases with relevant clinical consequences and potential therapeutic implications. In the present review, we update and summarize the clinical significance of copeptin as a surrogate marker for AVP concentrations in different kidney diseases, as well as in renal replacement therapy (hemodialysis and peritoneal dialysis) and renal transplantation.
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Affiliation(s)
- Pedro Iglesias
- Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
- Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, Madrid, Spain.
- Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
| | - Ramona A Silvestre
- Department of Clinical Biochemistry, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
- Department of Physiology, Medical School, Universidad Autónoma de Madrid, Madrid, Spain
| | | | - Juan J Díez
- Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
- Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, Madrid, Spain
- Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
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18
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Relation of Alcohol Intake to Kidney Function and Mortality Observational, Population-Based, Cohort Study. Nutrients 2022; 14:nu14061297. [PMID: 35334954 PMCID: PMC8954827 DOI: 10.3390/nu14061297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/13/2022] [Accepted: 03/16/2022] [Indexed: 12/10/2022] Open
Abstract
Data are conflicting about the effects of alcohol intake on kidney function. This population-based study investigated associations of alcohol intake with kidney function and mortality. The study cohort included adult participants in Exam-1, Exam-2 (6-year follow-up), and Exam-3 (20-year follow-up) of the Gubbio study. Kidney function was evaluated as estimated glomerular filtration rate (eGFR, CKD-Epi equation, mL/min × 1.73 m2). Daily habitual alcohol intake was assessed by questionnaires. Wine intake accounted for >94% of total alcohol intake at all exams. Alcohol intake significantly tracked over time (R > 0.66, p < 0.001). Alcohol intake distribution was skewed at all exams (skewness > 2) and was divided into four strata for analyses (g/day = 0, 1−24, 25−48, and >48). Strata of alcohol intake differed substantially for lab markers of alcohol intake (p < 0.001). In multivariable regression, strata of alcohol intake related cross-sectionally to eGFR at all exams (Exam-1: B = 1.70, p < 0.001; Exam-2: B = 1.03, p < 0.001; Exam-3: B = 0.55, p = 0.010) and related longitudinally to less negative eGFR change from Exam-1 to Exam-2 (B = 0.133, p = 0.002) and from Exam-2 to Exam-3 (B = 0.065, p = 0.004). In multivariable Cox models, compared to no intake, intakes > 24 g/day were not associated with different mortality while an intake of 1−24 g/day was associated with lower mortality in the whole cohort (HR = 0.77, p = 0.003) and in the subgroup with eGFR < 60 mL/min × 1.73 m2 (HR = 0.69, p = 0.033). These data indicate a positive independent association of alcohol intake with kidney function not due to a mortality-related selection.
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19
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Boo HJ, Lee JE, Chung SM, Jang HR, Huh W, Kim DJ, Kim YG. The presence of simple renal cysts is associated with an increased risk of albuminuria in young adults. Korean J Intern Med 2022; 37:425-433. [PMID: 34865415 PMCID: PMC8925965 DOI: 10.3904/kjim.2020.576] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 02/04/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIMS The prevalence of simple renal cysts increases with age; however, they are occasionally found in adults aged < 40 years. This cross-sectional study evaluated the clinical significance of simple cysts in young adults, focusing on their associations with hematuria and albuminuria. METHODS Adults aged < 40 years who underwent comprehensive medical examination between January 2005 and December 2013 were included. Simple renal cysts were identified by ultrasonography. RESULTS Renal cysts were found in 276 of the 5,832 subjects (4.7%). Subjects with medullary sponge kidney (n = 1) or polycystic kidney disease (n = 5) were excluded. A single cyst and multiple cysts were found in 234 (4.0%) and 42 (0.7%) subjects, respectively. Age, high systolic blood pressure, and history of hypertension were independent risk factors for the presence of simple cysts. Simple cysts were not associated with an increased prevalence of hematuria. However, subjects with cysts showed a higher prevalence of albuminuria than those without (11.3% vs. 4.5%, p < 0.001). Multivariate analysis revealed that the existence of simple renal cysts was associated with a 2.30-fold increased prevalence of albuminuria (95% confidence interval, 1.512 to 3.519; p < 0.001) independent of other risk factors. CONCLUSION In young adults, the presence of simple renal cysts was independently associated with an increased prevalence of albuminuria. The causal relationship needs to be elucidated in further studies.
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Affiliation(s)
- Hyo Jin Boo
- Division of Nephrology, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Jung Eun Lee
- Division of Nephrology, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Son Mi Chung
- Department of Medicine, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Hye Ryoun Jang
- Division of Nephrology, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Wooseong Huh
- Division of Nephrology, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Dae Joong Kim
- Division of Nephrology, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Yoon-Goo Kim
- Division of Nephrology, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
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20
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Hosseini R, Montazerifar F, Shahraki E, Karajibani M, Mokhtari AM, Dashipour AR, Ferns GA, Jalali M. The Effects of Zinc Sulfate Supplementation on Serum Copeptin, C-Reactive Protein and Metabolic Markers in Zinc-Deficient Diabetic Patients on Hemodialysis: A Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res 2022; 200:76-83. [PMID: 33655432 DOI: 10.1007/s12011-021-02649-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 02/18/2021] [Indexed: 11/25/2022]
Abstract
We aimed to investigate the association between zinc (Zn) supplementation and serum levels of copeptin, high-sensitive C-reactive protein (hs-CRP), glycemic control, anthropometric parameters and renal function in Zn -deficient diabetic hemodialysis patients (DHPs). This randomized, double-blind, placebo-controlled trial (RCT) was conducted on 46 DHPs with Zn-deficiency. The Zn supplement group (n = 21) received a 220-mg/day Zn sulfate capsule (containing 50 mg Zn), and the control group (n = 25) received a placebo capsule (220 mg corn starch), for 8 weeks. Fasting, predialysis blood samples were taken at baseline and after 8 weeks to assess fasting blood glucose (FBG), serum insulin, copeptin, high-sensitive C-reactive protein (hs-CRP), blood urea nitrogen (BUN), creatinine (Cr) concentrations, and homoeostatic model assessment (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Compared to controls, serum copeptin (P < 0.001), hs-CRP (P < 0.001), BUN (P < 0.001), Cr (P < 0.001), Zn (P < 0.001), FBG (P < 0.001) levels, BMI (P < 0.001), and body weight (P < 0.001) were significantly affected following ZnSO4 supplementation for 8 weeks. In contrast, QUICKI (P = 0.57), HOMA-IR (P = 0.60), and serum insulin (P = 0.55) were not affected following Zn supplementation in comparison with patients receiving placebo. Zn sulfate supplementation appears to have favorable effects on serum copeptin and hs-CRP, FBG, and renal function in Zn-deficient DHPs. Iranian Registry of Clinical Trials Identifier: IRCT20190806044461N1.
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Affiliation(s)
- Razieh Hosseini
- Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Farzaneh Montazerifar
- Pregnancy Health Research Center, Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Elham Shahraki
- Genetics of Non-Communicable Disease Research Center, Department of Nephrology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mansour Karajibani
- Health Promotion Research Center , Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Ali Mohammad Mokhtari
- School of Health, Gonabad University of Medical Sciences, Gonabad, Khorasan Razavi, Iran
| | - Ali Reza Dashipour
- Cellular and Molecular Research Center, Department of Food and Technology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK
| | - Mohammad Jalali
- Nutrition Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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21
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Investigation of possible underlying mechanisms behind water-induced glucose reduction in adults with high copeptin. Sci Rep 2021; 11:24481. [PMID: 34966186 PMCID: PMC8716535 DOI: 10.1038/s41598-021-04224-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/17/2021] [Indexed: 11/12/2022] Open
Abstract
Elevated copeptin, a surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk. Water supplementation in habitual low-drinkers with high copeptin significantly lowers both fasting plasma (fp) copeptin and glucose. This study aims at investigating possible underlying mechanisms. Thirty-one healthy adults with high copeptin (> 10.7 pmol·L−1 (men), > 6.1 pmol−1 (women)) and 24-h urine volume of < 1.5L and osmolality of > 600 mOsm·kg−1 were included. The intervention consisted of addition of 1.5 L water daily for 6 weeks. Fp-adrenocorticotropic hormone (ACTH), fp-cortisol, 24-h urine cortisol, fasting and 2 h (post oral glucose) insulin and glucagon were not significantly affected by the water intervention. However, decreased (Δ baseline-6 weeks) fp-copeptin was significantly associated with Δfp-ACTH (r = 0.76, p < 0.001) and Δfp-glucagon (r = 0.39, p = 0.03), respectively. When dividing our participants according to baseline copeptin, median fp-ACTH was reduced from 13.0 (interquartile range 9.2–34.5) to 7.7 (5.3–9.9) pmol L−1, p = 0.007 in the top tertile of copeptin, while no reduction was observed in the other tertiles. The glucose lowering effect from water may partly be attributable to decreased activity in the hypothalamic–pituitary–adrenal axis. ClinicalTrials.gov: NCT03574688.
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22
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Jacques PF, Rogers G, Stookey JD, Perrier ET. Water Intake and Markers of Hydration Are Related to Cardiometabolic Risk Biomarkers in Community-Dwelling Older Adults: A Cross-Sectional Analysis. J Nutr 2021; 151:3205-3213. [PMID: 34383920 PMCID: PMC8485913 DOI: 10.1093/jn/nxab233] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 06/14/2021] [Accepted: 06/22/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Emerging evidence links underhydration and habitual low water intake to higher cardiometabolic risk, but evidence is limited in community-dwelling older adults. OBJECTIVES The objective is to examine if higher water intake and better hydration are associated with better cardiometabolic health. METHODS This cross-sectional analysis using general linear models included 2238 participants from the Framingham Heart Study Second Generation and First Generation Omni cohorts with an estimated glomerular filtration rate >30 mL·min-1·1.73 m-2 and a valid FFQ for assessment of water intake. Of these participants, 2219 had fasting spot urinary creatinine data and 950 had 24-h urine creatinine data to assess hydration. Cardiometabolic risk factors included fasting glucose, triglycerides (TGs), total cholesterol (TC), HDL cholesterol, and calculated LDL cholesterol; glycated hemoglobin (HbA1c); C-reactive protein (CRP); and systolic (SBP) and diastolic (DBP) blood pressure. RESULTS The combined cohorts were on average aged 70 y; 55% were women. Mean (95% CI) daily total water intakes were 2098 (2048, 2150) mL for men and 2109 (2063, 2156) mL for women. Total daily water, beverage (including plain water), and plain water intakes demonstrated significant positive trends with HDL cholesterol (P < 0.01). TG concentrations were significantly lower among the highest plain water consumers (P < 0.05). The 24-h urine concentration, as measured by creatinine, was positively associated with LDL cholesterol and TG concentrations ( P < 0.01) and inversely associated with HDL cholesterol concentrations (P < 0.002). Neither water intake nor urine concentration was associated with glucose or HbA1c (P > 0.05). CONCLUSIONS Our findings of a consistent pattern between circulating lipid concentrations and different water sources and hydration markers support an association between hydration and lipid metabolism in older adults and add to the growing evidence that inadequate water intake and underhydration may lead to higher cardiometabolic risk.
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Affiliation(s)
- Paul F Jacques
- USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - Gail Rogers
- USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | | | - Erica T Perrier
- Health, Hydration & Nutrition Science, Danone Research, Palaiseau, France
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23
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Go S, Kim S, Son HE, Ryu JY, Yang H, Choi SR, Seo JW, Jo YH, Koo JR, Baek SH. Association between copeptin levels and treatment responses to hypertonic saline infusion in patients with symptomatic hyponatremia: a prospective cohort study. Kidney Res Clin Pract 2021; 40:371-382. [PMID: 34233437 PMCID: PMC8476303 DOI: 10.23876/j.krcp.20.233] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 04/28/2021] [Indexed: 11/05/2022] Open
Abstract
Background Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients. Methods We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24–48 hours and copeptin levels at baseline/24 hours were analyzed. Results Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02). Conclusion There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.
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Affiliation(s)
- Suryeong Go
- Department of Internal Medicine, Armed Forces Yangju Hospital, Yangju, Republic of Korea
| | - Sejoong Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hyung-Eun Son
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Ji-Young Ryu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Huijin Yang
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea
| | - Sun Ryoung Choi
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea
| | - Jang-Won Seo
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea
| | - You Hwan Jo
- Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Ja-Ryong Koo
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea
| | - Seon Ha Baek
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea
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24
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Wang HW, Jiang MY. Higher volume of water intake is associated with lower risk of albuminuria and chronic kidney disease. Medicine (Baltimore) 2021; 100:e26009. [PMID: 34011099 PMCID: PMC8137104 DOI: 10.1097/md.0000000000026009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 04/30/2021] [Indexed: 01/05/2023] Open
Abstract
Increased water intake correlated to lower vasopressin level and may benefit kidney function. However, results of previous studies were conflicted and inconclusive. We aimed to investigate the association between water intake and risk of chronic kidney disease (CKD) and albuminuria.In this cross-sectional study, the study population were adult participants of 2011-2012 National Health and Nutrition Examination Survey (NHANES) whose estimated glomerular filtration rate (eGFR) were ≥30 ml/min/1.73 m2. Data of water intake were obtained from the NHANES 24-h dietary recall questionnaire. Participants were divided into three groups based on volume of water intake: <500 (low, n = 1589), ≥500 to <1200 (moderate, n = 1359), and ≥1200 ml/day (high, n = 1685). CKD was defined as eGFR <60 ml/min/1.73 m2, and albuminuria as albumin-to-creatinine ratio (ACR) ≥30 mg/g.Our results showed that 377 out of 4633 participants had CKD; the prevalence inversely correlated to volume of water intake: 10.7% in low, 8.2% in moderate, and 5.6% in high intake groups (P < .001). Prevalence of albuminuria was also lower in high (9.5%) compared with moderate (12.8%) and low intake groups (14.1%), P < .001. Additionally, water intake positively correlated to eGFR and negatively correlated to urinary ACR, as well as plasma and urine osmolality. Multivariable logistic regression showed that low water intake group had higher risk of CKD (OR 1.35, 95% CI 1.01-1.82) and albuminuria when compared to high water intake group (OR 1.42, 95% CI 1.13-1.79).In conclusion, increased water intake was associated lower risk of CKD and albuminuria. Meticulous studies are needed to elucidate the underlying mechanisms.
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Sodium Intake and Proteinuria/Albuminuria in the Population-Observational, Cross-Sectional Study. Nutrients 2021; 13:nu13041255. [PMID: 33920400 PMCID: PMC8068813 DOI: 10.3390/nu13041255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/02/2021] [Accepted: 04/09/2021] [Indexed: 02/07/2023] Open
Abstract
Sodium effects on proteinuria are debated. This observational, cross-sectional, population-based study investigated relationships to proteinuria and albuminuria of sodium intake assessed as urinary sodium/creatinine ratio (NaCR). In 482 men and 454 women aged 35–94 years from the Moli-sani study, data were collected for the following: urinary NaCR (independent variable); urinary total proteins/creatinine ratio (PCR, mg/g), urinary albumin/creatinine ratio (ACR, mg/g), and urinary non-albumin-proteins/creatinine ratio (calculated as PCR minus ACR) (dependent variables). High values were defined as PCR ≥ 150 mg/g, ACR ≥ 30 mg/g, and urinary non-albumin-proteins/creatinine ratio ≥ 120 mg/g. Urinary variables were measured in first-void morning urine. Skewed variables were log-transformed in analyses. The covariates list included sex, age, energy intake, body mass index, waist/hip ratio, estimated urinary creatinine excretion, smoking, systolic pressure, diastolic pressure, diabetes, history of cardiovascular disease, reported treatment with antihypertensive drug, inhibitor or blocker of the renin-angiotensin system, diuretic, and log-transformed data of total physical activity, leisure physical activity, alcohol intake, and urinary ratios of urea nitrogen, potassium, and phosphorus to creatinine. In multivariable linear regression, standardized beta coefficients of urinary NaCR were positive with PCR (women and men = 0.280 and 0.242, 95% confidence interval = 0.17/0.39 and 0.13/0.35, p < 0.001), ACR (0.310 and 0.265, 0.20/0.42 and 0.16/0.38, p < 0.001), and urinary non-albumin-proteins/creatinine ratio (0.247 and 0.209, 0.14/0.36 and 0.09/0.33, p < 0.001). In multivariable logistic regression, higher quintile of urinary NaCR associated with odds ratio of 1.81 for high PCR (1.55/2.12, p < 0.001), 0.51 of 1.62 for high ACR (1.35/1.95, p < 0.001), and of 1.84 for high urinary non-albumin proteins/creatinine ratio (1.58/2.16, p < 0.001). Findings were consistent in subgroups. Data indicate independent positive associations of an index of sodium intake with proteinuria and albuminuria in the population.
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Selective afferent renal denervation mitigates renal and splanchnic sympathetic nerve overactivity and renal function in chronic kidney disease-induced hypertension. J Hypertens 2021; 38:765-773. [PMID: 31764582 DOI: 10.1097/hjh.0000000000002304] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Clinical and experimental evidence have shown that renal denervation, by removing both the sympathetic and afferent nerves, improves arterial hypertension and renal function in chronic kidney disease (CKD). Given the key role of renal sympathetic innervation in maintaining sodium and water homeostasis, studies have indicated that the total removal of renal nerves leads to impaired compensatory mechanisms during hemodynamic challenges. METHOD In the present study, we hypothesized that afferent (or sensory) fibers from the diseased kidney contribute to sympathetic overactivation to the kidney and other target organ, such as the splanchnic region, contributing to hypertension in CKD. We used a method to remove selectively the afferent renal fibers (periaxonal application of 33 mmol/l capsaicin) in a rat model of CKD, the 5/6 nephrectomy. RESULTS Three weeks after afferent renal denervation (ARD), we found a decrease in mean arterial pressure (∼15%) and normalization in renal and splanchnic sympathetic nerve hyperactivity in the CKD group. Interestingly, intrarenal renin--angiotensin system, as well as renal fibrosis and function and proteinuria were improved after ARD in CKD rats. CONCLUSION The findings demonstrate that afferent fibers contribute to the maintenance of arterial hypertension and reduced renal function that are likely to be mediated by increased sympathetic nerve activity to the renal territory as well as to other target organs in CKD.
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Perrier ET, Armstrong LE, Bottin JH, Clark WF, Dolci A, Guelinckx I, Iroz A, Kavouras SA, Lang F, Lieberman HR, Melander O, Morin C, Seksek I, Stookey JD, Tack I, Vanhaecke T, Vecchio M, Péronnet F. Hydration for health hypothesis: a narrative review of supporting evidence. Eur J Nutr 2020; 60:1167-1180. [PMID: 32632658 PMCID: PMC7987589 DOI: 10.1007/s00394-020-02296-z] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 05/28/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE An increasing body of evidence suggests that excreting a generous volume of diluted urine is associated with short- and long-term beneficial health effects, especially for kidney and metabolic function. However, water intake and hydration remain under-investigated and optimal hydration is poorly and inconsistently defined. This review tests the hypothesis that optimal chronic water intake positively impacts various aspects of health and proposes an evidence-based definition of optimal hydration. METHODS Search strategy included PubMed and Google Scholar using relevant keywords for each health outcome, complemented by manual search of article reference lists and the expertise of relevant practitioners for each area studied. RESULTS The available literature suggest the effects of increased water intake on health may be direct, due to increased urine flow or urine dilution, or indirect, mediated by a reduction in osmotically -stimulated vasopressin (AVP). Urine flow affects the formation of kidney stones and recurrence of urinary tract infection, while increased circulating AVP is implicated in metabolic disease, chronic kidney disease, and autosomal dominant polycystic kidney disease. CONCLUSION In order to ensure optimal hydration, it is proposed that optimal total water intake should approach 2.5 to 3.5 L day-1 to allow for the daily excretion of 2 to 3 L of dilute (< 500 mOsm kg-1) urine. Simple urinary markers of hydration such as urine color or void frequency may be used to monitor and adjust intake.
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Affiliation(s)
- Erica T Perrier
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France.
| | - Lawrence E Armstrong
- Department of Kinesiology, University of Connecticut, Storrs, CT, USA.,Hydration & Nutrition, LLC, Newport News, VA, USA
| | - Jeanne H Bottin
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - William F Clark
- London Health Sciences Centre and Western University, London, ON, Canada
| | - Alberto Dolci
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - Isabelle Guelinckx
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - Alison Iroz
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - Stavros A Kavouras
- College of Health Solutions and Hydration Science Lab, Arizona State University, Phoenix, AZ, USA
| | - Florian Lang
- Department of Physiology, Eberhard Karls University, Tübingen, Germany
| | | | - Olle Melander
- Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Clementine Morin
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - Isabelle Seksek
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - Jodi D Stookey
- Children's Hospital Oakland Research Institute, Oakland, CA, USA
| | - Ivan Tack
- Explorations Fonctionnelles Physiologiques, Hôpital Rangueil, Toulouse, France
| | - Tiphaine Vanhaecke
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - Mariacristina Vecchio
- Health, Hydration & Nutrition Science, Danone Research, Route Départementale 128, 91767, Palaiseau cedex, France
| | - François Péronnet
- École de Kinésiologie et des Sciences de l'activité Physique, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
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Butler-Dawson J, Dally M, Johnson RJ, Johnson EC, Krisher L, Sánchez-Lozada LG, Griffin BR, Brindley S, Newman LS. Association of Copeptin, a Surrogate Marker of Arginine Vasopressin, with Decreased Kidney Function in Sugarcane Workers in Guatemala. ANNALS OF NUTRITION AND METABOLISM 2020; 76:30-36. [PMID: 32172243 DOI: 10.1159/000506619] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/16/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and to examine whether higher fluid intake is associated with lower circulating copeptin and thereby preserves kidney health among sugarcane workers exposed to hot conditions. METHODS Utilizing a longitudinal study of 105 workers in Guatemala, we examined relationships between hydration indices, plasma copeptin concentrations, and kidney function markers at 3 times during the 6-month harvest. We also examined whether baseline copeptin concentrations increased the odds of developing an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS Copeptin concentrations were positively associated with serum creatinine (β 1.41, 95% CI 0.88-2.03) and negatively associated with eGFR (β -1.07, 95% CI -1.43 to -0.70). In addition, as workers improved their hydration (measured by increases in fluid balance), copeptin concentrations were reduced, and this reduction was associated with an improvement in kidney function. CONCLUSIONS Results suggest that copeptin should be studied as a potential prognostic biomarker.
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Affiliation(s)
- Jaime Butler-Dawson
- Center for Health, Work, and Environment, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA, .,Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA, .,Colorado Consortium on Climate Change and Human Health, University of Colorado, Aurora, Colorado, USA,
| | - Miranda Dally
- Center for Health, Work, and Environment, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.,Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.,Colorado Consortium on Climate Change and Human Health, University of Colorado, Aurora, Colorado, USA
| | - Richard J Johnson
- Colorado Consortium on Climate Change and Human Health, University of Colorado, Aurora, Colorado, USA.,Division of Renal Diseases and Hypertension, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA
| | - Evan C Johnson
- Division of Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA
| | - Lyndsay Krisher
- Center for Health, Work, and Environment, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.,Colorado Consortium on Climate Change and Human Health, University of Colorado, Aurora, Colorado, USA
| | | | - Benjamin R Griffin
- Division of Renal Diseases and Hypertension, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado, USA
| | - Stephen Brindley
- Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA
| | - Lee S Newman
- Center for Health, Work, and Environment, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.,Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.,Colorado Consortium on Climate Change and Human Health, University of Colorado, Aurora, Colorado, USA.,Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, Aurora, Colorado, USA.,Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA
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Wiromrat P, Bjornstad P, Vinovskis C, Chung LT, Roncal C, Pyle L, Lanaspa MA, Johnson RJ, Cherney DZ, Reznick-Lipina TK, Bishop F, Maahs DM, Wadwa RP. Elevated copeptin, arterial stiffness, and elevated albumin excretion in adolescents with type 1 diabetes. Pediatr Diabetes 2019; 20:1110-1117. [PMID: 31433534 PMCID: PMC7151746 DOI: 10.1111/pedi.12909] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 07/18/2019] [Accepted: 08/08/2019] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE We sought to evaluate copeptin concentrations in adolescents with and without type 1 diabetes (T1D) and examine the associations between copeptin and measures of arterial stiffness and kidney dysfunction. RESEARCH DESIGN AND METHODS This analysis included 169 adolescents with T1D (12-19 years of age, 59% girls, mean HbA1c 9.0 ± 1.5% and diabetes duration of 8.6 ± 2.9 years), in addition to 61 controls without T1D. Arterial stiffness including carotid-femoral pulse wave velocity (CF-PWV), carotid-radial PWV (CR-PWV), augmentation index normalized to heart rate of 75 bpm (AIx@HR75), and brachial artery distensibility (BAD). Serum copeptin, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C were also assessed. RESULTS Compared to controls, adolescents with T1D had higher median (Q1-Q3) copeptin (7.5 [5.2-11.3] vs 6.4 [4.8-8.3] pmol/L, P = .01), mean ± SD eGFR (121 ± 23 vs 112 ± 16 mL/min/1.73m2 , P = .002) and lower BAD (7.1 ± 1.3 vs 7.2 ± 1.2%, P = .02). Adolescents with T1D in the in high tertile copeptin group (>9.1 pmol/L) had higher AIx@HR75 (10.7 ± 1.2 vs 5 ± 1.2, P = .001), CR-PWV (5.30 ± 1.0 vs 5.18 ± 1.0 m/s, P = .04), and UACR (12 ± 1 vs 8 ± 1 mg/g, P = .025) compared to those in low tertile (<5.8 pmol/L) after adjusting for age, sex, and eGFR. Copeptin inversely associated with CF-PWV independent of age, sex, eGFR, SBP, and HbA1c in T1D adolescents. CONCLUSIONS Our data demonstrate that elevated copeptin was associated with worse arterial stiffness in adolescents with T1D. These findings suggest that copeptin could improve CVD risk stratification in adolescents with T1D.
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Affiliation(s)
- Pattara Wiromrat
- Section of Endocrinology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Petter Bjornstad
- Section of Endocrinology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, United States,Section of Nephrology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Carissa Vinovskis
- Section of Endocrinology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Linh T. Chung
- Section of Endocrinology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Carlos Roncal
- Section of Nephrology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Laura Pyle
- Section of Endocrinology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado, United States,Department of Biostatistics and Informatics, University of Colorado Denver School of Public Health, Aurora, Colorado, United States
| | - Miguel A. Lanaspa
- Section of Nephrology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Richard J. Johnson
- Section of Nephrology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - David Z. Cherney
- Department of Nephrology, University of Toronto School of Medicine, Ontario, Canada
| | - Tyler K. Reznick-Lipina
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - Franziska Bishop
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
| | - David M. Maahs
- Section of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California,Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA
| | - R. Paul Wadwa
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
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Chang DC, Basolo A, Piaggi P, Votruba SB, Krakoff J. Hydration biomarkers and copeptin: relationship with ad libitum energy intake, energy expenditure, and metabolic fuel selection. Eur J Clin Nutr 2019; 74:158-166. [PMID: 31160665 PMCID: PMC6888878 DOI: 10.1038/s41430-019-0445-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 05/17/2019] [Accepted: 05/21/2019] [Indexed: 12/17/2022]
Abstract
Background/Objective Evidence from non-human species indicate that hydration and arginine vasopressin (AVP) influence fuel selection, energy expenditure (EE), and food intake, but these relationships are unclear in humans. We sought to assess whether hydration biomarkers [24-h urine volume (UVol) and urine urea nitrogen concentration (UUN)] and copeptin (a surrogate for AVP) are associated with 24-h EE, respiratory quotient (RQ), and daily energy intake (DEI). Subjects/Methods In a secondary analysis of collected data, we selected healthy adults (Group 1, n = 177) who had 24-h whole-room indirect calorimetry measurements in energy balance with 24-h urine collection and fasting copeptin measurements (n=117), followed by 3 days ad libitum food intake. A separate group (Group 2, n=284) with hydration markers and calorimetry measurements was also studied. The main outcome measures were 24-h RQ, 24-h EE, DEI, substrate oxidation. Results In Group 1, lower 24-h UVol and higher 24-h UUN, indicating lower hydration, were correlated with lower 24-h RQ (r = 0.35, p <0.0001, and r = −0.29, p = 0.0001, respectively; results similar in Group 2) and predicted subsequent reduced DEI (r = 0.20, p = 0.01, and r = −0.27, p = 0.0003, respectively), adjusted for confounders. Copeptin was independently associated with 24-h lipid oxidation (r = −0.23, p = 0.01). In Group 2, lower hydration was associated with reduced 24-h EE (24-h UVol: r = 0.29, p <0.0001; 24-h UUN: r = −0.25, p <0.0001). Conclusions Hydration biomarkers were associated with metabolic differences characterized by altered food intake, fuel selection, and possibly EE. Independently, copeptin was associated with higher lipid oxidation.
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Affiliation(s)
- Douglas C Chang
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
| | - Alessio Basolo
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA
| | - Paolo Piaggi
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA
| | - Susanne B Votruba
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA
| | - Jonathan Krakoff
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA
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Ranieri M, Di Mise A, Tamma G, Valenti G. Vasopressin-aquaporin-2 pathway: recent advances in understanding water balance disorders. F1000Res 2019; 8. [PMID: 30800291 PMCID: PMC6364380 DOI: 10.12688/f1000research.16654.1] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/23/2019] [Indexed: 12/11/2022] Open
Abstract
The alteration of water balance and related disorders has emerged as being strictly linked to the state of activation of the vasopressin–aquaporin-2
(vasopressin–AQP2) pathway. The lack of responsiveness of the kidney to the vasopressin action impairs its ability to concentrate the urine, resulting in polyuria, polydipsia, and risk of severe dehydration for patients. Conversely, non-osmotic release of vasopressin is associated with an increase in water permeability in the renal collecting duct, producing water retention and increasing the circulatory blood volume. This review highlights some of the new insights and recent advances in therapeutic intervention targeting the dysfunctions in the vasopressin–AQP2 pathway causing diseases characterized by water balance disorders such as congenital nephrogenic diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, nephrogenic syndrome of inappropriate antidiuresis, and autosomal dominant polycystic kidney disease. The recent clinical data suggest that targeting the vasopressin–AQP2 axis can provide therapeutic benefits in patients with water balance disorders.
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Affiliation(s)
- Marianna Ranieri
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy, 70125, Italy
| | - Annarita Di Mise
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy, 70125, Italy
| | - Grazia Tamma
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy, 70125, Italy.,Istituto Nazionale di Biostrutture e Biosistemi, Rome, Roma, Italy, 00136, Italy
| | - Giovanna Valenti
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy, 70125, Italy.,Istituto Nazionale di Biostrutture e Biosistemi, Rome, Roma, Italy, 00136, Italy.,Center of Excellence in Comparative Genomics (CEGBA), University of Bari, Bari, Italy, 70125, Italy
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Chen J, Ma X, Xu D, Cao W, Kong X. Association between simple renal cyst and kidney damage in a Chinese cohort study. Ren Fail 2019. [PMID: 31282239 PMCID: PMC6691781 DOI: 10.1080/0886022x.2019.1632718] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Background: The presence of simple renal cyst (SRC) has been associated to renal dysfunction, but the results were inconsistent. Accordingly, we conducted a longitudinal cohort study to explore the association between SRC and kidney damage. Methods: A total of 4274 adults (aged 45.4 ± 13.6 years) without chronic kidney disease at baseline were enrolled in 2008. SRC was assessed by ultrasonography. Logistic regression analysis were applied to explore the relationships between SRC and indicators of kidney damage (proteinuria and renal insufficiency), and also with relatively rapid decline in renal function (defined as the lowest quartile of △eGFR). Results: During 5 years of follow-up, participants in the SRC group had higher incidence of proteinuria (5.2% versus 2.4%, p = 0.004) and renal insufficiency (3.8% versus 0.97%, p < 0.001) compared with control group. SRC was correlated with proteinuria (OR 2.24; 95% CI 1.34–3.75) and renal insufficiency (OR 4.0; 95% CI 2.11–7.58) in univariable analysis, despite that the correlation was not significant after adjusted for traditional kidney disease risk factors. Furthermore, after adjusted for potential confounders, maximum diameter of the cyst (≥2.2 cm) was significantly associated with rapid decline in renal function (OR 2.19; 95% CI 1.24–3.87). Conclusions: Participants with SRC may be associated with higher incidence of proteinuria and renal insufficiency. This relationship may be obscured by age and other traditional risk factors. Higher diameter of the cysts contributed to more rapid decline in renal function of SRC participants.
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Affiliation(s)
- Juan Chen
- Department of Nephrology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, China
| | - Xiaojing Ma
- Health Screening Center, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, China
| | - Dongmei Xu
- Department of Nephrology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, China
| | - Wei Cao
- Department of Nephrology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, China
| | - Xianglei Kong
- Department of Nephrology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, China
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Qian Q. Salt, water and nephron: Mechanisms of action and link to hypertension and chronic kidney disease. Nephrology (Carlton) 2018; 23 Suppl 4:44-49. [PMID: 30298656 PMCID: PMC6221012 DOI: 10.1111/nep.13465] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/30/2018] [Indexed: 12/27/2022]
Abstract
Our knowledge on sodium and water homeostasis and regulation continues to evolve. A considerable amount of new information in this area has emerged in recent years. This review summarizes existing and new literature and discusses complex multi-organ effects of high-salt and low-water intake and role of arginine vasopressin in this process, as well as the potential clinical significance of non-osmotic sodium storage pool and rhythmicity of urine sodium excretion. It has become clear that sodium and water dysregulation can exert profound effects on kidney and vascular health, far greater than previously recognized. Maladaptation to a combined high-salt and low-water intake can be linked to the growing epidemic of hypertension and chronic kidney disease.
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Affiliation(s)
- Qi Qian
- Division of Nephrology and Hypertension, Department of Medicine, Mayo ClinicCollege of MedicineRochesterUSA
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Velho G, Ragot S, El Boustany R, Saulnier PJ, Fraty M, Mohammedi K, Fumeron F, Potier L, Marre M, Hadjadj S, Roussel R. Plasma copeptin, kidney disease, and risk for cardiovascular morbidity and mortality in two cohorts of type 2 diabetes. Cardiovasc Diabetol 2018; 17:110. [PMID: 30071874 PMCID: PMC6071392 DOI: 10.1186/s12933-018-0753-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 07/26/2018] [Indexed: 12/15/2022] Open
Abstract
Background Cardiovascular disease and kidney damage are tightly associated in people with type 2 diabetes. Experimental evidence supports a causal role for vasopressin (or antidiuretic hormone) in the development of diabetic kidney disease (DKD). Plasma copeptin, the COOH-terminal portion of pre-provasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the development and progression of DKD. Here we assessed the association of plasma copeptin with the risk of cardiovascular events during follow-up in two prospective cohorts of type 2 diabetic patients, and we examined if this association could be mediated by deleterious effects of vasopressin on the kidney. Methods We studied 3098 and 1407 type 2 diabetic patients from the French cohorts DIABHYCAR and SURDIAGENE, respectively. We considered the incidence during follow-up (median: 5 years) of a combined end point composed of myocardial infarction, coronary revascularization, hospitalization for congestive heart failure, or cardiovascular death. Copeptin concentration was measured in baseline plasma samples by an immunoluminometric assay. Results The cumulative incidence of cardiovascular events during follow-up by sex-specific tertiles of baseline plasma copeptin was 15.6% (T1), 18.7% (T2) and 21.7% (T3) in DIABHYCAR (p = 0.002), and 27.7% (T1), 34.1% (T2) and 47.6% (T3) in SURDIAGENE (p < 0.0001). Cox proportional hazards survival regression analyses confirmed the association of copeptin with cardiovascular events in both cohorts: hazard ratio with 95% confidence interval for T3 vs. T1 was 1.29 (1.04–1.59), p = 0.02 (DIABHYCAR), and 1.58 (1.23–2.04), p = 0.0004 (SURDIAGENE), adjusted for sex, age, BMI, duration of diabetes, systolic blood pressure, arterial hypertension, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, estimated glomerular filtration rate (eGFR), urinary albumin concentration (UAC), active tobacco smoking, and previous history of myocardial infarction at baseline. No interaction was observed between plasma copeptin and eGFR (p = 0.40) or UAC (p = 0.61) categories on the risk of cardiovascular events in analyses of pooled cohorts. Conclusions Plasma copeptin was positively associated with major cardiovascular events in people with type 2 diabetes. This association cannot be solely accounted for by the association of copeptin with kidney-related traits. Electronic supplementary material The online version of this article (10.1186/s12933-018-0753-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Gilberto Velho
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.
| | - Stéphanie Ragot
- INSERM, CIC 0802, Poitiers, France.,UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France
| | - Ray El Boustany
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France
| | - Pierre-Jean Saulnier
- INSERM, CIC 0802, Poitiers, France.,UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France.,INSERM, Research Unit 1082, Poitiers, France
| | | | - Kamel Mohammedi
- Service d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, France.,Faculté de Médecine Paul Broca, Université de Bordeaux, Bordeaux, France
| | - Frédéric Fumeron
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
| | - Louis Potier
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
| | - Michel Marre
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
| | - Samy Hadjadj
- INSERM, CIC 0802, Poitiers, France.,UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France.,INSERM, Research Unit 1082, Poitiers, France.,Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
| | - Ronan Roussel
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'École de Médecine, Paris, 75006, France.,Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France
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35
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El Boustany R, Tasevska I, Meijer E, Kieneker LM, Enhörning S, Lefèvre G, Mohammedi K, Marre M, Fumeron F, Balkau B, Bouby N, Bankir L, Bakker SJ, Roussel R, Melander O, Gansevoort RT, Velho G. Plasma copeptin and chronic kidney disease risk in 3 European cohorts from the general population. JCI Insight 2018; 3:121479. [PMID: 29997293 PMCID: PMC6124520 DOI: 10.1172/jci.insight.121479] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 05/23/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function. Here, we evaluated the association of plasma copeptin, a surrogate of vasopressin, with the incidence of CKD in the general population. METHODS We studied 3 European cohorts: DESIR (n = 5,047; France), MDCS-CC (n = 3,643; Sweden), and PREVEND (n = 7,684; the Netherlands). Median follow-up was 8.5, 16.5, and 11.3 years, respectively. Pooled data were analyzed at an individual level for 4 endpoints during follow-up: incidence of stage 3 CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2); the KDIGO criterion "certain drop in eGFR"; rapid kidney function decline (eGFR slope steeper than -3 ml/min/1.73 m2/yr); and incidence of microalbuminuria. RESULTS The upper tertile of plasma copeptin was significantly and independently associated with a 49% higher risk for stage 3 CKD (P < 0.0001); a 64% higher risk for kidney function decline, as defined by the KDIGO criterion (P < 0.0001); a 79% higher risk for rapid kidney function decline (P < 0.0001); and a 24% higher risk for microalbuminuria (P = 0.008). CONCLUSIONS High copeptin levels are associated with the development and the progression of CKD in the general population. Intervention studies are needed to assess the potential beneficial effect on kidney health in the general population of reducing vasopressin secretion or action. FUNDING INSERM and Danone Research Centre for Specialized Nutrition.
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Affiliation(s)
- Ray El Boustany
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- Danone Nutricia Research, Palaiseau, France
| | - Irina Tasevska
- Departments of Internal Medicine and Clinical Sciences, Lund University, Malmö, Sweden
| | - Esther Meijer
- Department of Internal Medicine, University Medical Center, Division of Nephrology, University of Groningen, Groningen, Netherlands
| | - Lyanne M. Kieneker
- Department of Internal Medicine, University Medical Center, Division of Nephrology, University of Groningen, Groningen, Netherlands
| | - Sofia Enhörning
- Departments of Internal Medicine and Clinical Sciences, Lund University, Malmö, Sweden
| | - Guillaume Lefèvre
- Service de Biochimie et Hormonologie, Assistance Publique — Hôpitaux de Paris, Hôpitaux Universitaires Est Parisien–Tenon, Paris, France
| | - Kamel Mohammedi
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- Department of Diabetology, Endocrinology and Nutrition, DHU Fire, Assistance Publique — Hôpitaux de Paris, Bichat Hospital, Paris, France
| | - Michel Marre
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- Department of Diabetology, Endocrinology and Nutrition, DHU Fire, Assistance Publique — Hôpitaux de Paris, Bichat Hospital, Paris, France
- UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Frédéric Fumeron
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Beverley Balkau
- Inserm Research Unit 1018, Center for Research in Epidemiology and Population Health, Villejuif, France
- Université Paris Sud, Villejuif, France
| | - Nadine Bouby
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Lise Bankir
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- UPMC University Paris 6, Sorbonne Universités, Paris, France
| | - Stephan J.L. Bakker
- Department of Internal Medicine, University Medical Center, Division of Nephrology, University of Groningen, Groningen, Netherlands
| | - Ronan Roussel
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
- Department of Diabetology, Endocrinology and Nutrition, DHU Fire, Assistance Publique — Hôpitaux de Paris, Bichat Hospital, Paris, France
- UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Olle Melander
- Departments of Internal Medicine and Clinical Sciences, Lund University, Malmö, Sweden
| | - Ron T. Gansevoort
- Department of Internal Medicine, University Medical Center, Division of Nephrology, University of Groningen, Groningen, Netherlands
| | - Gilberto Velho
- Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France
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Qian Q. Dietary Influence on Body Fluid Acid-Base and Volume Balance: The Deleterious "Norm" Furthers and Cloaks Subclinical Pathophysiology. Nutrients 2018; 10:E778. [PMID: 29914153 PMCID: PMC6024597 DOI: 10.3390/nu10060778] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/08/2018] [Accepted: 06/12/2018] [Indexed: 02/07/2023] Open
Abstract
The popular modern diet, characterized by an excess of animal protein and salt but insufficient in fruits, vegetables and water, is a poor fit for human physiological and homeostatic regulatory systems. Sustained net acid and sodium retention, coupled with an insufficient intake of cardiovascular protective potassium-rich foods and hydration in the modern diet can give rise to debilitating chronic organ dysfunction and ultimately, mortality. This holds true, especially in our aging population who are already facing inevitable decline in organ functional reserve. Importantly, in most cases, despite the mismatch and adverse effects to multiple organ systems, plasma electrolyte and acid-base parameters can, on the surface, be maintained within a “normal” reference range, primarily by activating (often maximally activating) compensatory homeostatic mechanisms. These diet-induced effects can thus be clinically silent for decades. Embodied in the chronic corrective homeostatic processes, however, are real risks for multiorgan damage. According to the Dietary Guideline Advisory Committee (DGAC), half of American adults have one or more chronic diseases that are preventable with dietary modification. Here, homeostasis of body fluid acid-base, sodium, potassium and water is examined. Our current dietary habits and their required regulatory adaptation, maladaptation and relevant physiology and pathophysiology are discussed. A framework of dietary modifications to avoid a propensity for maladaptation and thus lowers the risks of common modern diseases (primary prevention) and minimizes the risk of chronic and age-related disease progression (secondary prevention) is emphasized. Although there are other variables at play, a key to restoring the all-important dietary potassium to sodium ratio is greater consumption of vegetables/fruits and adopting salt temperance. Dietary and nutritional optimization is an under-emphasized area of health care that has an enormous potential to temper the epidemics of prevalent chronic diseases in modern society and improve population health.
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Affiliation(s)
- Qi Qian
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, School of Medicine, Rochester, MN 55905, USA.
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37
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Effect of Chronic Kidney Disease on Changes in Vasopressin System Expression in the Kidney Cortex in Rats with Nephrectomy. BIOMED RESEARCH INTERNATIONAL 2018; 2018:2607928. [PMID: 30013980 PMCID: PMC6022316 DOI: 10.1155/2018/2607928] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 04/18/2018] [Accepted: 05/21/2018] [Indexed: 02/01/2023]
Abstract
It is believed that the vasopressinergic system plays an important role in the pathogenesis of chronic kidney disease (CKD). The aim of this study was to evaluate the effect of CKD on changes in vasopressin system expression in the kidney cortex in rats with nephrectomy. The study was performed on 4 groups of Sprague Dawley (SPRD) rats: a control group (CN), 1/2 nephrectomy (N1/2), 2/3 nephrectomy (N2/3), and 5/6 nephrectomy (N5/6). Blood and the kidney cortex were collected to evaluate plasma copeptin concentrations and mRNA expressions of V1a vasopressin receptors (V1aR) and V2 vasopressin receptors (V2R) and V1aR, V2R, and aquaporin 2 (AQP2) protein levels. V1aR and V2R mRNA expression in the kidney cortex was significantly lower in the CN group compared with the other groups. In contrast, the V1aR, V2R, and AQP2 protein levels were significantly higher in the CN group compared with all of the nephrectomized groups. Plasma copeptin concentration was significantly lower in the CN group than in the nephrectomized groups. CKD caused significant changes in the expression of the vasopressinergic system. Further research is needed to explain the mechanisms of the impact of the vasopressinergic system on the kidney in CKD.
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38
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Kong X, Ma X, Zhang C, Su H, Gong X, Xu D. Increased risk of kidney damage among Chinese adults with simple renal cyst. Int Urol Nephrol 2018; 50:1687-1694. [PMID: 29728991 DOI: 10.1007/s11255-018-1880-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/23/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND The presence of simple renal cyst (SRC) has been related to hypertension, the early and long-term allograft function, and aortic disease, but the relationship with kidney damage was still controversial. Accordingly, we conducted a large sample cross-sectional study to explore the association of SRC with indicators of kidney damage among Chinese adults. METHODS A total of 42,369 adults (aged 45.8 ± 13.67 years, 70.6% males) who visited the Health Checkup Clinic were consecutively enrolled. SRC was assessed by ultrasonography according to Bosniak category. Multiple regression models were applied to explore the relationships between SRC and indicators of kidney damage [proteinuria (dipstick urine protein ≥ 1+) and decreased estimated glomerular filtration rate (DeGFR) < 60 ml/min/1.73 m2]. RESULTS Among all participants in the study, the prevalence of SRC was 10.5%. As a categorical outcome, participants with more 1 cyst and with 1 cyst had higher percentage of proteinuria [53 (5.3%) and 93 (2.7%) vs. 596 (1.6%), p < 0.001] and DeGFR [57 (5.7%) and 85 (2.5%) vs. 278 (0.7%), p < 0.001] compared with participants with no cyst. SRC significantly correlated with proteinuria [OR 1.59 (95% CI 1.30-1.95)] and DeGFR [OR 1.97 (95% CI 1.56-2.47)] after adjusting for potential confounders. Furthermore, the results also demonstrated that maximum diameter (per 1 cm increase), bilateral location, and multiple cysts significantly correlated with DeGFR in the multiple logistic regression analysis. CONCLUSIONS The study revealed that SRC significantly correlated with kidney damage and special attention should be paid among Chinese adults with SRC.
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Affiliation(s)
- Xianglei Kong
- Department of Nephrology, Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China
| | - Xiaojing Ma
- Department of Health Examination Center, Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, People's Republic of China
| | - Chengyin Zhang
- Department of Nephrology, Yidu Central Hospital, Weifang Medical College, No. 4138, South Road of Linglong Mountain, Qingzhou, People's Republic of China
| | - Hong Su
- Department of Nephrology, Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China
| | - Xiaojie Gong
- Department of Nephrology, Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China
| | - Dongmei Xu
- Department of Nephrology, Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, People's Republic of China.
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39
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Tasneem M, Mannix C, Wong A, Zhang J, Rangan G. Is serum copeptin a modifiable biomarker in autosomal dominant polycystic kidney disease? World J Nephrol 2018; 7:51-57. [PMID: 29527508 PMCID: PMC5838414 DOI: 10.5527/wjn.v7.i2.51] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 01/29/2018] [Accepted: 02/28/2018] [Indexed: 02/06/2023] Open
Abstract
The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]. However, serum copeptin is strongly correlated with creatinine, and its additional value as a prognostic biomarker over estimated glomerular filtration rate and TKV is not certain. It has also been suggested that copeptin could be a predictive biomarker to select ADPKD patients who are most likely to benefit from AVP-modifying therapies, but prospective data to validate this assumption are required. In this regard, long-term randomised clinical trials evaluating the effect of prescribed water intake on renal cyst growth may contribute to addressing this hypothesis. In conclusion, although serum copeptin is aligned with the basic pathogenesis of ADPKD, further rigorous studies are needed to define if it will contribute to enabling the delivery of personalised care in ADPKD.
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Affiliation(s)
- Moomal Tasneem
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Carly Mannix
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Annette Wong
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Jennifer Zhang
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
| | - Gopala Rangan
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney 2145, Australia
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40
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Copeptin Plasma Levels are Associated with Decline of Renal Function in Patients with Type 2 Diabetes Mellitus. Arch Med Res 2018; 49:36-43. [DOI: 10.1016/j.arcmed.2018.04.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 04/06/2018] [Indexed: 12/21/2022]
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41
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Suthahar N, Meijers WC, Brouwers FP, Heerspink HJL, Gansevoort RT, van der Harst P, Bakker SJL, de Boer RA. Heart failure and inflammation-related biomarkers as predictors of new-onset diabetes in the general population. Int J Cardiol 2017; 250:188-194. [PMID: 29074040 DOI: 10.1016/j.ijcard.2017.10.035] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 09/15/2017] [Accepted: 10/09/2017] [Indexed: 01/17/2023]
Abstract
BACKGROUND There is a strong reciprocal relationship between heart failure (HF) and diabetes mellitus (DM). Shared pathophysiological mechanisms might be a possible explanation. Therefore, we hypothesised that biomarkers linked to HF would also predict new-onset type 2 DM in the general population. METHODS AND RESULTS We utilized the Prevention of Vascular and Renal End-stage Disease (PREVEND) cohort (mean age 48.9years, 51% female) to study the relationship between HF and DM in 7953 participants free of baseline HF and DM. Multiple HF-related, inflammation-related and renal function-related biomarkers were evaluated regarding their predictive utility in new-onset DM. Incidence of DM in participants who developed HF was 11.8%, versus 5.4% in those who had not developed HF (p<0.001). Incidence of HF in participants who developed DM was 8.5%, versus 3.8% in those who had not developed DM (p<0.001). Classical HF biomarkers, NT-proBNP and hs-TnT were not associated with an increased risk for new-onset DM. However, inflammatory biomarkers hs-CRP [hazard ratio (HR) 1.16, (95% CI 1.05 to 1.29), p=0.005], procalcitonin [HR 1.34, (95% CI 1.07 to 1.69), p=0.012] and PAI-1 [HR 1.55, (95% CI 1.37 to 1.75), p<0.001] remained significantly associated with new-onset DM, even after multivariable adjustment for established predictors of DM. CONCLUSIONS Although HF and DM have a strong correlation with each other, systemic biomarkers that predict HF do not have a predictive value in new-onset DM. This suggests that other, indirect, pathophysiological mechanisms related to inflammation may explain their strong relation.
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Affiliation(s)
- Navin Suthahar
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Wouter C Meijers
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Frank P Brouwers
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Ron T Gansevoort
- Department of Nephrology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Pim van der Harst
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Nephrology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Rudolf A de Boer
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
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Clark WF, Devuyst O, Roussel R. The vasopressin system: new insights for patients with kidney diseases: Epidemiological evidence and therapeutic perspectives. J Intern Med 2017; 282:310-321. [PMID: 28905441 DOI: 10.1111/joim.12654] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
People with chronic kidney disease (CKD) are at risk of severe outcomes, such as end-stage renal disease or cardiovascular disease, and CKD is a globally increasing health burden with a high personal and economic cost. Despite major progresses in prevention and therapeutics in last decades, research is still needed to reverse this epidemic trend. The regulation of water balance and the state of activation of the vasopressin system have emerged as factors tightly associated with kidney health, in the general population but also in specific conditions; among them, various stages of CKD, diabetes and autosomal dominant polycystic kidney disease (ADPKD). Basic science findings and also epidemiological evidence have justified important efforts towards interventional studies supporting causality, and opening therapeutic avenues. On the basis of recent clinical data, the blockade of V2 vasopressin receptors using tolvaptan in patients with rapidly progressing ADPKD has been granted in several countries, and a long-term randomized trial evaluating the effect of an increase in water intake in patients with CKD is on-going.
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Affiliation(s)
- W F Clark
- Division of Nephrology, Department of Medicine, London Health Sciences Centre, London, ON, Canada
| | - O Devuyst
- Institute of Physiology, University of Zurich, Zurich, Switzerland
| | - R Roussel
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.,Département de Diabétologie, Endocrinologie et Nutrition, Assistance Publique Hôpitaux de Paris, Hôpital Bichat, DHU FIRE, Paris, France.,Sorbonne Paris Cite, UFR de Médecine, Université Paris Diderot, Paris, France
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43
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Zittema D, van den Brand JAJG, Bakker SJL, Wetzels JF, Gansevoort RT. Copeptin, a surrogate marker for arginine vasopressin, is associated with disease severity and progression in IgA nephropathy patients. Nephrol Dial Transplant 2017; 32:i146-i153. [PMID: 28057871 DOI: 10.1093/ndt/gfw391] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 10/10/2016] [Indexed: 12/12/2022] Open
Abstract
Background Besides its essential role for water homeostasis, arginine vasopressin (AVP) may have deleterious effects on the kidney. Copeptin, a surrogate marker for AVP, has been shown to be related to renal outcome in patients with diabetic nephropathy and polycystic kidney disease. We investigated the association of copeptin with disease severity and progression in immunoglobulin A nephropathy (IgAN). Methods We included a prospective cohort of 59 patients with biopsy proven IgAN. Urinary excretion of α1 microglobulin (α1m), β 2 microglobulin (β2m), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and total protein were measured at baseline. Plasma copeptin was determined from stored baseline serum samples. Cox regression was performed for the composite renal outcome defined as doubling of serum creatinine, end-stage renal disease (ESRD) or start of immunosuppressive therapy, and for the individual components during 5-year follow-up. Results In IgAN patients [male: 72%, age: 42 ± 13 years, mean arterial pressure (MAP): 101 ± 12 mmHg, proteinuria: 1.4 (0.7-2.3) g/day, estimated glomerular filtration rate (eGFR): 48 ± 21 mL/min/1.73 m 2 ] median copeptin was 9.4 (5.3-18.4) pmol/L. At baseline, copeptin was associated with α1m [standardized beta (St. β) = 0.34, P = 0.009], β2m (St. β = 0.33, P = 0.01) and proteinuria (St. β = 0.36, P = 0.053), adjusted for sex and eGFR. During follow-up, the highest tertile of baseline copeptin was positively associated with the incidence of the composite renal outcome as well as with the individual components of doubling of creatinine, ESRD and start of immunosuppressive therapy. In Cox regression models, copeptin showed prognostic value over MAP, proteinuria and eGFR for the composite renal outcome. Conclusions Copeptin is associated with disease severity and prognosis in IgAN patients and may have additional prognostic value besides established risk markers.
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Affiliation(s)
- Debbie Zittema
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan A J G van den Brand
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Stephan J L Bakker
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jack F Wetzels
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ron T Gansevoort
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Johar D, Bernstein L. A targeted approach toward more accurate assessment of hypertension. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2017. [DOI: 10.1016/j.ejcdt.2017.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Abstract
Copeptin is derived from the cleavage of the precursor of arginine vasopressin (AVP), produced in an equimolar ratio in hypothalamus and processed during axonal transport AVP is an unstable peptide and has a short half-life of 5-20 min. Unlike AVP, copeptin is a stable molecule and can easily be measured. Recent evidence suggest that increased copeptin levels have been associated with worse outcomes in various clinical conditions including chronic kidney disease (CKD) and hypertension. In this review, the data regarding copeptin with kidney function (evaluated as glomerular filtration rate, increased albumin/protein excretion or both) and hypertension with regard to performed studies, prognosis and pathogenesis was summarised.
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Youhanna S, Bankir L, Jungers P, Porteous D, Polasek O, Bochud M, Hayward C, Devuyst O. Validation of Surrogates of Urine Osmolality in Population Studies. Am J Nephrol 2017; 46:26-36. [PMID: 28586769 PMCID: PMC6080694 DOI: 10.1159/000475769] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 04/12/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (Uosm), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. METHODS We analyzed 2 possible surrogates of Uosm in 4 large population-based cohorts (total n = 4,247) and in patients with chronic kidney disease (CKD, n = 146). An estimated Uosm (eUosm) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured Uosm (mUosm). RESULTS eUosm is an excellent surrogate of mUosm, with a highly significant linear relationship and values within 5% of mUosm (r = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eUosm and mUosm with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mUosm is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mUosm in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mUosm. CONCLUSION The eUosm is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function.
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Affiliation(s)
- Sonia Youhanna
- Institute of Physiology, University of Zurich, Zurich, Switzerland
| | - Lise Bankir
- INSERM UMRS 1138, Centre de Recherche des Cordeliers, Paris, France
- Université Pierre et Marie Curie, Paris, France
| | - Paul Jungers
- Service de Néphrologie, Hôpital Necker, Paris, France
| | - David Porteous
- Centre for Genomic & Experimental Medicine, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland
| | - Ozren Polasek
- Department of Public Health, Universityof Split, Split, Croatia
| | - Murielle Bochud
- Institute of Social and Preventive Medicine, Lausanne University Hospital Center, Lausanne, Switzerland
| | - Caroline Hayward
- MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland
| | - Olivier Devuyst
- Institute of Physiology, University of Zurich, Zurich, Switzerland
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El Boustany R, Taveau C, Chollet C, Velho G, Bankir L, Alhenc-Gelas F, Roussel R, Bouby N. Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of diabetic nephropathy in a mouse model of type 2 diabetes. J Diabetes Complications 2017; 31:929-932. [PMID: 28412033 DOI: 10.1016/j.jdiacomp.2017.04.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 02/07/2017] [Accepted: 04/03/2017] [Indexed: 02/04/2023]
Abstract
AIMS Vasopressin is increased in diabetes and was shown to contribute to development of diabetic nephropathy through V2 receptor (V2R) activation in an experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains undocumented. This study addresses the issue in a mouse model of type 2 diabetes. METHODS Male obese diabetic db/db mice were treated for 12weeks with a selective V2R antagonist (SR121463) and compared to non-treated db/db and non-diabetic db/m mice. All animals were previously uninephrectomized. RESULTS The V2R antagonist did not alter glycemia or glycosuria in db/db mice. It induced a two-fold increase in urine output and a 52% decrease in urine osmolality compared to non-treated db/db mice. After four weeks of treatment urinary albumin to creatinine ratio was 50% lower in treated mice compared to non-treated mice, and remained significantly lower until end of experiment. Glomerular filtration rate increased significantly over time in non-treated db/db mice but remained stable in treated mice. CONCLUSIONS This study shows that vasopressin contributes to albuminuria and glomerular hyperfiltration via V2R in a mouse model of type 2 diabetes. It documents causality behind the association of vasopressin with renal disease observed in diabetic patients.
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Affiliation(s)
- Ray El Boustany
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Danone Research-R&D Waters, Hydration and Health Dept., Palaiseau, France
| | - Christopher Taveau
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Université Paris Descartes, Paris, France
| | - Catherine Chollet
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Université Paris Descartes, Paris, France
| | - Gilberto Velho
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France
| | - Lise Bankir
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Université Paris Descartes, Paris, France
| | - François Alhenc-Gelas
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Université Paris Descartes, Paris, France
| | - Ronan Roussel
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Université Paris Diderot, Paris, France; Département de Diabétologie-Endocrinologie-Nutrition, DHU FIRE, Hôpital Bichat, AP-HP, Paris, France
| | - Nadine Bouby
- INSERM, UMRS_1138, Centre de Recherche des Cordeliers, Paris, France; Université Pierre & Marie Curie, Paris, France; Université Paris Descartes, Paris, France.
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The Effect of Renal Function and Hemodialysis Treatment on Plasma Vasopressin and Copeptin Levels. Kidney Int Rep 2017; 2:410-419. [PMID: 29142968 PMCID: PMC5678637 DOI: 10.1016/j.ekir.2017.01.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 12/21/2016] [Accepted: 01/13/2017] [Indexed: 12/18/2022] Open
Abstract
Introduction Copeptin is increasingly used in epidemiological studies as a substitute for vasopressin. The effect of renal function per se on copeptin and vasopressin concentrations as well as their ratio have, however, not been well described. Methods Copeptin and vasopressin levels were measured in 127 patients with various stages of chronic kidney disease, including 42 hemodialysis patients and 16 healthy participants in this observational study. Linear (segmental) regression analyses were performed to assess the association between renal function and copeptin, vasopressin and the C/V ratio. In addition, clearance of copeptin and vasopressin by hemodialysis was calculated. Results Both copeptin and vasopressin levels were higher when renal function was lower, and both showed associations with plasma osmolality. The C/V ratio was stable across renal function in subjects with an eGFR >28 ml/min per 1.73 m2. In contrast, the C/V ratio increased with worsening renal function in patients with eGFR ≤28 ml/min per 1.73 m2. During hemodialysis, the initial decrease in vasopressin levels was greater compared with copeptin and, consequently, the C/V ratio increased. This was, at least in part, explained by a greater dialytic clearance of vasopressin compared with copeptin. Discussion Our data indicate that copeptin is a reliable substitute for vasopressin in subjects with an eGFR >28 ml/min per 1.73 m2, whereas at an eGFR ≤28 ml/min per 1.73 m2, that is, CKD stages 4 and 5, a correction for renal function is required in epidemiological studies that use copeptin as a marker for vasopressin. Intradialytic copeptin levels do not adequately reflect vasopressin levels because vasopressin clearance by hemodialysis is higher than that of copeptin.
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Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study. PLoS One 2017; 12:e0169137. [PMID: 28081152 PMCID: PMC5231381 DOI: 10.1371/journal.pone.0169137] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 12/12/2016] [Indexed: 12/19/2022] Open
Abstract
Background Epidemics of chronic kidney disease (CKD) not due to diabetes mellitus (DM) or hypertension have been observed among individuals working in hot environments in several areas of the world. Experimental models have documented that recurrent heat stress and water restriction can lead to CKD, and the mechanism may be mediated by hyperosmolarity that activates pathways (vasopressin, aldose reductase-fructokinase) that induce renal injury. Here we tested the hypothesis that elevated serum sodium, which reflects serum osmolality, may be an independent risk factor for the development of CKD. Methods This study was a large-scale, single-center, retrospective 5-year cohort study at Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, between 2004 and 2009. We analyzed 13,201 subjects who underwent annual medical examination of which 12,041 subjects (age 35 to 85) without DM and/or CKD were enrolled. This analysis evaluated age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, hyperuricemia, fasting glucose, BUN, serum sodium, potassium, chloride and calculated serum osmolarity. Results Elevated serum sodium was an independent risk factor for development of CKD (OR: 1.03, 95% CI, 1.00–1.07) after adjusted regression analysis with an 18 percent increased risk for every 5 mmol/L change in serum sodium. Calculated serum osmolarity was also an independent risk factor for CKD (OR: 1.04; 95% CI, 1.03–1.05) as was BUN (OR: 1.08; 95% CI, 1.06–1.10) (independent of serum creatinine). Conclusions Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD. This finding supports the role of limiting salt intake and preventing dehydration to reduce risk of CKD.
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