Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics
María Dolores Arenas Jimenez, Emilio González-Parra, Marta Riera, Abraham Rincón Bello, Ana López-Herradón, Higini Cao, Sara Hurtado, Silvia Collado, Laura Ribera, Francesc Barbosa, Fabiola Dapena, Vicent Torregrosa, José-Jesús Broseta, Carlos Soto Montañez, Juan F Navarro-González, Rosa Ramos, Jordi Bover, Xavier Nogués-Solan, Marta Crespo, Adriana S Dusso, Julio Pascual
Nutrients, doi:10.3390/nu13082559
Background. In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17. 1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. Conclusions.
References
Alfieri, Regalia, Zanoni, Vettoretti, Cozzolino et al., The Importance of Adherence in the Treatment of Secondary Hyperparathyroidism, Blood Purif,
doi:10.1159/000492918Ali, Role of vitamin D in preventing of COVID-19 infection, progression and severity, J. Infect. Public Health
Arcidiacono, Yang, Fernandez, Dusso, The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfu311Arenas, Crespo, Pérez-Sáez, Collado, Redondo-Pachón et al., Clinical Profiles in Renal Patients with COVID-19, J. Clin. Med,
doi:10.3390/jcm9082665Atchison, Ortiz-Capisano, Beierwaltes, Acute activation of the calcium-sensing receptor inhibits plasma renin activity in vivo, Am. J. Physiol. Regul. Integr. Comp. Physiol,
doi:10.1152/ajpregu.00238.2010Autier, Mullie, Macacu, Dragomir, Boniol et al., Effect of vitamin D supplementation on non-skeletal disorders: A systematic review of meta-analyses and randomised trials, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(17)30357-1Carpagnano, Di Lecce, Quaranta, Zito, Buonamico et al., Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19, J. Endocrinol. Investig,
doi:10.1007/s40618-020-01370-xCastillo, Costa, Barrios, Díaz, Miranda et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2020.105751Chertow, Plone, Dillon, Burke, Slatopolsky, Hyperparathyroidism and dialysis vintage, Clin. Nephrol
Cucinotta, Vanelli, WHO Declares COVID-19 a Pandemic, Acta Biomed
Cui, Xu, Li, Qiao, Han et al., Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system, Redox Biol,
doi:10.1016/j.redox.2019.101295Dancer, Parekh, Lax, D'souza, Zheng et al., Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS), Thorax,
doi:10.1136/thoraxjnl-2014-206680Dijkman, Jebbink, Deijs, Milewska, Pyrc et al., Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63, J. Gen. Virol,
doi:10.1099/vir.0.043919-0Gassen, Niemeyer, Muth, Corman, Martinelli et al., SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection, Nat. Commun,
doi:10.1038/s41467-019-13659-4Goicoechea, Cámara, Macías, De Morales, Rojas et al., COVID-19: Clinical course and outcomes of 36 hemodialysis patients in Spain, Kidney Int,
doi:10.1016/j.kint.2020.04.031Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients,
doi:10.3390/nu12040988Guerrero, De Oca, Aguilera-Tejero, Zafra, Rodriguez et al., The effect of vitamin D derivatives on vascular calcification associated with inflammation, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfr555Han, Li, Yang, King, Xiao et al., Counter-regulatory paracrine actions of FGF-23 and 1,25(OH)2D in macrophages, FEBS Lett,
doi:10.1002/1873-3468.12040Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab. Syndr
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2011-0385Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin. Exp. Res,
doi:10.1007/s40520-020-01570-8Isakova, Wahl, Vargas, Gutiérrez, Scialla et al., Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease, Kidney Int,
doi:10.1038/ki.2011.47Jean, Souberbielle, Chazot, Vitamin D in Chronic Kidney Disease and Dialysis Patients, Nutrients,
doi:10.3390/nu9040328Jolliffe, Stefanidis, Wang, Kermani, Dimitrov et al., Vitamin D Metabolism Is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease, Am. J. Respir. Crit. Care Med,
doi:10.1164/rccm.201909-1867OCLeifheit-Nestler, Grabner, Hermann, Richter, Schmitz et al., Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfw454Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data, BMJ,
doi:10.1136/bmj.i6583Mcgonagle, Sharif, O'regan, Bridgewood, The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease, Autoimmun. Rev,
doi:10.1016/j.autrev.2020.102537Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results, JAMA Netw. Open,
doi:10.1001/jamanetworkopen.2021.4117Merzon, Tworowski, Gorohovski, Vinker, Cohen et al., Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: An Israeli population-based study, FEBS J,
doi:10.1111/febs.15495Moe, Chertow, Parfrey, Kubo, Block et al., Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial, Circulation,
doi:10.1161/CIRCULATIONAHA.114.013876Ostroverkhova, Hu, Tarasov, Melnikova, Porozov et al., Calcium-Sensing Receptor and Regulation of WNK Kinases in the Kidney, Cells,
doi:10.3390/cells9071644Palau, Riera, Soler, ADAM17 inhibition may exert a protective effect on COVID-19, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfaa093Panizo, Carrillo-López, Naves-Díaz, Solache-Berrocal, Martínez-Arias et al., Regulation of miR-29b and miR-30c by vitamin D receptor activators contributes to attenuate uraemia-induced cardiac fibrosis, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfx060Patel, Clarke, Wang, Fan, Parajuli et al., Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: A positive feedback mechanism in the RAS, J. Mol. Cell. Cardiol,
doi:10.1016/j.yjmcc.2013.11.017Pilz, Zittermann, Trummer, Theiler-Schwetz, Lerchbaum et al., Vitamin D testing and treatment: A narrative review of current evidence, Endocr. Connect,
doi:10.1530/EC-18-0432Riera, Anguiano, Clotet, Ho, Rebull et al., Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria, Am. J. Physiol. Renal Physiol,
doi:10.1152/ajprenal.00082.2015Rincón, Moreso, López-Herradón, Fernández-Robres, Cidraque et al., The keys to control a COVID-19 outbreak in a haemodialysis unit, Clin. Kidney J,
doi:10.1093/ckj/sfaa119Rodriguez-Morales, Cardona-Ospina, Gutiérrez-Ocampo, Villamizar-Peña, Holguin-Rivera et al., Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis, Travel Med. Infect. Dis,
doi:10.1016/j.tmaid.2020.101623Rossaint, Oehmichen, Van Aken, Reuter, Pavenstädt et al., FGF23 signaling impairs neutrophil recruitment and host defense during CKD, J. Clin. Investig,
doi:10.1172/JCI83470Sodhi, Wohlford-Lenane, Yamaguchi, Prindle, Fulton et al., Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration, Am. J. Physiol. Lung Cell. Mol. Physiol,
doi:10.1152/ajplung.00498.2016Sánchez-Álvarez, Pérez Fontán, Jiménez Martín, Pelícano, Reina et al., SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN), Nefrologia,
doi:10.1016/j.nefro.2020.04.002Teng, Wolf, Lowrie, Ofsthun, Lazarus et al., Survival of Patients Undergoing Hemodialysis with Paricalcitol or Calcitriol Therapy, N. Engl. J. Med,
doi:10.1056/NEJMoa022536Torregrosa, Bover, Andía, Lorenzo, De Francisco et al., Recomendaciones de la Sociedad Española de Nefrología para el manejo de las alteraciones del metabolismo óseo-mineral en los pacientes con enfermedad renal crónica (S.E.N.-MM), Nefrologia
Wolf, Shah, Gutierrez, Ankers, Monroy et al., Vitamin D levels and early mortality among incident hemodialysis patients, Kidney Int,
doi:10.1038/sj.ki.5002451Wu, Leung, Leung, Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: A modelling study, Lancet,
doi:10.1016/S0140-6736(20)30260-9Xu, Yang, Chen, Luo, Zhang et al., Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system, Mol. Med. Rep,
doi:10.3892/mmr.2017.7546Zhang, Darssan, Pascoe, Johnson, Pi et al., Vitamin D status and mortality risk among patients on dialysis: A systematic review and meta-analysis of observational studies, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfy016Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target, Intensive Care Med,
doi:10.1007/s00134-020-05985-9Zheng, Peng, Xu, Zhao, Liu et al., Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis, J. Infect,
doi:10.1016/j.jinf.2020.04.021Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study, Lancet
{ 'indexed': {'date-parts': [[2024, 3, 20]], 'date-time': '2024-03-20T05:59:12Z', 'timestamp': 1710914352189},
'reference-count': 54,
'publisher': 'MDPI AG',
'issue': '8',
'license': [ { 'start': { 'date-parts': [[2021, 7, 26]],
'date-time': '2021-07-26T00:00:00Z',
'timestamp': 1627257600000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>Background. In COVID-19 patients, low serum vitamin D (VD) levels have been '
'associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis '
'(HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may '
'predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive '
'treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic '
'effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD '
'status and the administration of active vitamin D medications, used to treat secondary '
'hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A '
'cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 '
'in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers '
'in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). '
'Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D '
'(calcidiol) level was 17.1 [10.6–27.5] ng/mL and was not significantly associated to '
'mortality (OR 0.99 (0.97–1.01), p = 0.4). Patients receiving active vitamin D medications '
'(16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 '
'(32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < '
'0.001), and also those on both paricalcitol and calcimimetics, to treat secondary '
'hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower '
'mortality rate than patients receiving no treatment with either drug. Multivariate Cox '
'regression analysis confirmed this increased survival. Conclusions. Our findings suggest that '
'the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with '
'the improvement of survival in HD patients with COVID-19. No correlation was found between '
'serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies '
'and clinical trials are needed to support these findings.</jats:p>',
'DOI': '10.3390/nu13082559',
'type': 'journal-article',
'created': {'date-parts': [[2021, 7, 27]], 'date-time': '2021-07-27T02:22:46Z', 'timestamp': 1627352566000},
'page': '2559',
'source': 'Crossref',
'is-referenced-by-count': 10,
'title': 'Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics',
'prefix': '10.3390',
'volume': '13',
'author': [ {'given': 'María Dolores', 'family': 'Arenas Jimenez', 'sequence': 'first', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-0701-3969',
'authenticated-orcid': False,
'given': 'Emilio',
'family': 'González-Parra',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-4362-7965',
'authenticated-orcid': False,
'given': 'Marta',
'family': 'Riera',
'sequence': 'additional',
'affiliation': []},
{'given': 'Abraham', 'family': 'Rincón Bello', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ana', 'family': 'López-Herradón', 'sequence': 'additional', 'affiliation': []},
{'given': 'Higini', 'family': 'Cao', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sara', 'family': 'Hurtado', 'sequence': 'additional', 'affiliation': []},
{'given': 'Silvia', 'family': 'Collado', 'sequence': 'additional', 'affiliation': []},
{'given': 'Laura', 'family': 'Ribera', 'sequence': 'additional', 'affiliation': []},
{'given': 'Francesc', 'family': 'Barbosa', 'sequence': 'additional', 'affiliation': []},
{'given': 'Fabiola', 'family': 'Dapena', 'sequence': 'additional', 'affiliation': []},
{'given': 'Vicent', 'family': 'Torregrosa', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-4559-9083',
'authenticated-orcid': False,
'given': 'José-Jesús',
'family': 'Broseta',
'sequence': 'additional',
'affiliation': []},
{'given': 'Carlos', 'family': 'Soto Montañez', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-5015-7474',
'authenticated-orcid': False,
'given': 'Juan F.',
'family': 'Navarro-González',
'sequence': 'additional',
'affiliation': []},
{'given': 'Rosa', 'family': 'Ramos', 'sequence': 'additional', 'affiliation': []},
{'given': 'Jordi', 'family': 'Bover', 'sequence': 'additional', 'affiliation': []},
{'given': 'Xavier', 'family': 'Nogués-Solan', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-1852-2259',
'authenticated-orcid': False,
'given': 'Marta',
'family': 'Crespo',
'sequence': 'additional',
'affiliation': []},
{'given': 'Adriana S.', 'family': 'Dusso', 'sequence': 'additional', 'affiliation': []},
{'given': 'Julio', 'family': 'Pascual', 'sequence': 'additional', 'affiliation': []}],
'member': '1968',
'published-online': {'date-parts': [[2021, 7, 26]]},
'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30260-9'},
{ 'key': 'ref2',
'first-page': '157',
'article-title': 'WHO Declares COVID-19 a Pandemic',
'volume': '91',
'author': 'Cucinotta',
'year': '2020',
'journal-title': 'Acta Biomed.'},
{'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30183-5'},
{'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/nm1143'},
{'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30566-3'},
{'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.autrev.2020.102537'},
{'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jinf.2020.04.021'},
{'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/jcm9082665'},
{'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.kint.2020.04.031'},
{'key': 'ref10', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ckj/sfaa119'},
{'key': 'ref11', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40618-020-01370-x'},
{'key': 'ref12', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thoraxjnl-2014-206680'},
{'key': 'ref13', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.i6583'},
{'key': 'ref14', 'doi-asserted-by': 'publisher', 'DOI': '10.1164/rccm.201909-1867OC'},
{'key': 'ref15', 'doi-asserted-by': 'publisher', 'DOI': '10.1530/EC-18-0432'},
{'key': 'ref16', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00134-020-05985-9'},
{'key': 'ref17', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.kisu.2017.04.001'},
{ 'key': 'ref18',
'first-page': '3',
'article-title': 'Recomendaciones de la Sociedad Española de Nefrología para el manejo de '
'las alteraciones del metabolismo óseo-mineral en los pacientes con '
'enfermedad renal crónica (S.E.N.-MM)',
'volume': '31',
'author': 'Torregrosa',
'year': '2011',
'journal-title': 'Nefrologia'},
{'key': 'ref19', 'doi-asserted-by': 'publisher', 'DOI': '10.1210/jc.2011-0385'},
{'key': 'ref20', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu9040328'},
{'key': 'ref21', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.nefro.2020.04.002'},
{'key': 'ref22', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tmaid.2020.101623'},
{ 'key': 'ref23',
'first-page': '295',
'article-title': 'Hyperparathyroidism and dialysis vintage',
'volume': '54',
'author': 'Chertow',
'year': '2000',
'journal-title': 'Clin. Nephrol.'},
{'key': 'ref24', 'doi-asserted-by': 'publisher', 'DOI': '10.1159/000492918'},
{'key': 'ref25', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ndt/gfy016'},
{'key': 'ref26', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S2213-8587(17)30357-1'},
{'key': 'ref27', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu12040988'},
{'key': 'ref28', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40520-020-01570-8'},
{'key': 'ref29', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jiph.2020.06.021'},
{'key': 'ref30', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.dsx.2020.04.050'},
{'key': 'ref31', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/febs.15495'},
{'key': 'ref32', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamanetworkopen.2021.4117'},
{'key': 'ref33', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ndt/gfr555'},
{'key': 'ref34', 'doi-asserted-by': 'publisher', 'DOI': '10.1152/ajprenal.00082.2015'},
{'key': 'ref35', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ndt/gfw454'},
{'key': 'ref36', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ndt/gfx060'},
{'key': 'ref37', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2020.105751'},
{'key': 'ref38', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41467-019-13659-4'},
{'key': 'ref39', 'doi-asserted-by': 'publisher', 'DOI': '10.3892/mmr.2017.7546'},
{'key': 'ref40', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.redox.2019.101295'},
{'key': 'ref41', 'doi-asserted-by': 'publisher', 'DOI': '10.1099/vir.0.043919-0'},
{'key': 'ref42', 'doi-asserted-by': 'publisher', 'DOI': '10.1152/ajplung.00498.2016'},
{'key': 'ref43', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.yjmcc.2013.11.017'},
{'key': 'ref44', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/sj.ki.5002451'},
{'key': 'ref45', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa022536'},
{'key': 'ref46', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ndt/gfu311'},
{'key': 'ref47', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ndt/gfaa093'},
{'key': 'ref48', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/cells9071644'},
{'key': 'ref49', 'doi-asserted-by': 'publisher', 'DOI': '10.1152/ajpregu.00238.2010'},
{'key': 'ref50', 'doi-asserted-by': 'publisher', 'DOI': '10.1161/CIRCULATIONAHA.114.013876'},
{'key': 'ref51', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/ki.2011.47'},
{'key': 'ref52', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/1873-3468.12040'},
{'key': 'ref53', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30628-0'},
{'key': 'ref54', 'doi-asserted-by': 'publisher', 'DOI': '10.1172/JCI83470'}],
'container-title': 'Nutrients',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/13/8/2559/pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 7, 27]],
'date-time': '2021-07-27T17:01:55Z',
'timestamp': 1627405315000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/13/8/2559'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 7, 26]]},
'references-count': 54,
'journal-issue': {'issue': '8', 'published-online': {'date-parts': [[2021, 8]]}},
'alternative-id': ['nu13082559'],
'URL': 'http://dx.doi.org/10.3390/nu13082559',
'relation': {},
'ISSN': ['2072-6643'],
'subject': ['Food Science', 'Nutrition and Dietetics'],
'container-title-short': 'Nutrients',
'published': {'date-parts': [[2021, 7, 26]]}}
