Designing new diagnostic systems for the early detection of tobacco-associated chronic renal damage in patients of a primary care centre in Salamanca, Spain: an observational, prospective study protocol

Marta Prieto, Laura Vicente-Vicente, Alfredo G Casanova, Maria Teresa Hernández-Sánchez, Manuel A Gomez-Marcos, Luis Garcia-Ortiz, Ana Isabel Morales, members of the Biomarkers of kidney damage and tobacco, Moisés Pescador Garriel, Ángela de Cabo Laso, Jesús González Sánchez, Natalia Sánchez Aguadero, Carmela Rodríguez Martín, Benigna Sánchez Salgado, Cristina Agudo Conde, Cristina Lugones Sánchez, Miguel Ángel Hernández Mezquita, Miguel Barrueco Ferrero, Marta Prieto, Laura Vicente-Vicente, Alfredo G Casanova, Maria Teresa Hernández-Sánchez, Manuel A Gomez-Marcos, Luis Garcia-Ortiz, Ana Isabel Morales, members of the Biomarkers of kidney damage and tobacco, Moisés Pescador Garriel, Ángela de Cabo Laso, Jesús González Sánchez, Natalia Sánchez Aguadero, Carmela Rodríguez Martín, Benigna Sánchez Salgado, Cristina Agudo Conde, Cristina Lugones Sánchez, Miguel Ángel Hernández Mezquita, Miguel Barrueco Ferrero

Abstract

Introduction: Tobacco causes kidney damage that can progress to chronic kidney disease. However, the diagnostic parameters used in clinics are not effective in identifying smokers at risk. Our first objective is to more effectively detect subclinical renal damage in smokers. In addition, we hypothesise that tobacco consumption can predispose smokers to renal damage on exposure to other potentially nephrotoxic events (drugs, diagnostic procedures and so on). We will test this hypothesis in our second objective by investigating whether certain predisposition markers (GM2 ganglioside activator protein (GM2AP), transferrin and t-gelsolin) are able to detect smokers who are predisposed to kidney damage. Finally, in our third objective, we will study whether smoking cessation reduces subclinical and/or predisposition to renal damage.

Methods and analysis: For our first objective, a prospective cross-sectional study will be carried out with patients from a primary healthcare centre. The influence of tobacco on renal damage, in patients both with and without additional risk factors, will be studied using a panel of early biomarkers (albuminuria, N-acetyl-beta-D-glucosaminidase, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin). For our second objective, a prospective longitudinal study will be carried out with patients recruited for our first objective. We will study whether certain predisposition biomarkers (GM2AP, transferrin and t-gelsolin) are able to detect smokers predisposed to renal damage. For our third objective, a prospective longitudinal study will be carried out with patients from a smoking cessation unit. We will study the evolution of the markers described above following smoking cessation.

Ethics and dissemination: The study has been approved by the Clinical Research Ethics Committee of the Healthcare Area of Salamanca. All study participants will sign an informed consent form in compliance with the Declaration of Helsinki and the WHO standards for observational studies. Results will be presented at conferences and submitted to peer-reviewed journals.

Trial registration number: NCT03850756.

Keywords: biomarkers; kidney damage; tobacco.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design outline. Recruitment centres, patients’ distribution by groups, proposed objectives and specific biomarkers for each objective. CAUSA, University Hospital of Salamanca; GM2AP, GM2 ganglioside activator protein; KIM-1, kidney injury molecule-1; NAG, N-acetyl-beta-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; RF, risk factors.

References

    1. World Health Organization WHO report on the global tobacco epidemic 2015: raising taxes on tobacco, 2015. Available: [Accessed 4 May 2019].
    1. Whelton PK, Perneger TV, He J, et al. . The role of blood pressure as a risk factor for renal disease: a review of the epidemiologic evidence. J Hum Hypertens 1996;10:683–9.
    1. Pinto-Sietsma SJ, Mulder J, Janssen WM, et al. . Smoking is related to albuminuria and abnormal renal function in nondiabetic persons. Ann Intern Med 2000;133:585–91.10.7326/0003-4819-133-8-200010170-00008
    1. Orth SR. Smoking--a renal risk factor. Nephron 2000;86:12–26.10.1159/000045708
    1. Biesenbach G, Janko O, Zazgornik J. Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus. Nephrol Dial Transplant 1994;9:1097–102.10.1093/ndt/9.8.1097
    1. Hammer Y, Cohen E, Levi A, et al. . The relationship between cigarette smoking and renal function: a large cohort study. Isr Med Assoc J 2016;18:553–6.
    1. Stegmayr BG. A study of patients with diabetes mellitus (type 1) and end-stage renal failure: tobacco usage may increase risk of nephropathy and death. J Intern Med 1990;228:121–4.10.1111/j.1365-2796.1990.tb00204.x
    1. Rocco MV, Soucie JM, Reboussin DM, et al. . Risk factors for hospital utilization in chronic dialysis patients. southeastern kidney Council (network 6). J Am Soc Nephrol 1996;7:889–96.
    1. Vargas M. Documento Marco sobre Enfermedad Renal Crónica (ERC) dentro de la Estrategia de Abordaje a la Cronicidad en el SNS. Subdirección General De Calidad y Cohesión. Ministerio de Sanidad. Gobierno de España. Consejerías de Sanidad de las CCAA, 2015.
    1. Blank MD, Cobb CO, Kilgalen B, et al. . Acute effects of waterpipe tobacco smoking: a double-blind, placebo-control study. Drug Alcohol Depend 2011;116:102–9.10.1016/j.drugalcdep.2010.11.026
    1. Vaidya VS, Waikar SS, Ferguson MA, et al. . Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci 2008;1:200–8.10.1111/j.1752-8062.2008.00053.x
    1. Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol 2008;48:463–93.10.1146/annurev.pharmtox.48.113006.094615
    1. Bonventre JV, Vaidya VS, Schmouder R, et al. . Next-Generation biomarkers for detecting kidney toxicity. Nat Biotechnol 2010;28:436–40.10.1038/nbt0510-436
    1. Zhou Y, Vaidya VS, Brown RP, et al. . Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium. Toxicol Sci 2008;101:159–70.10.1093/toxsci/kfm260
    1. Jungbauer CG, Uecer E, Stadler S, et al. . N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: new predictors for long-term progression of chronic kidney disease in patients with heart failure. Nephrology (Carlton) 2016;21:490–8.10.1111/nep.12632
    1. Devarajan P. The use of targeted biomarkers for chronic kidney disease. Adv Chronic Kidney Dis 2010;17:469–79.10.1053/j.ackd.2010.09.002
    1. Vicente-Vicente L, Ferreira L, González-Buitrago JM, et al. . Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats. Toxicology 2013;304:83–91.10.1016/j.tox.2012.12.006
    1. Vicente-Vicente L, Sánchez-Juanes F, García-Sánchez O, et al. . Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase. Toxicol Lett 2015;234:99–109.10.1016/j.toxlet.2014.11.033
    1. Ferreira L, Quiros Y, Sancho-Martínez SM, et al. . Urinary levels of regenerating islet-derived protein III β and gelsolin differentiate gentamicin from cisplatin-induced acute kidney injury in rats. Kidney Int 2011;79:518–28.10.1038/ki.2010.439
    1. Quiros Y, Ferreira L, Sancho-Martínez SM, et al. . Sub-nephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein. Kidney Int 2010;78:1006–15.10.1038/ki.2010.267
    1. Gomez-Marcos MA, Martinez-Salgado C, Gonzalez-Sarmiento R, et al. . Association between different risk factors and vascular accelerated ageing (EVA study): study protocol for a cross-sectional, descriptive observational study. BMJ Open 2016;6:e01103110.1136/bmjopen-2016-011031
    1. Jaffe M. Ueber den Niederschlag welchen Pikrinsäure in normalen Harn erzeugt und über eine neue reaction des Kreatinins. Z Physiol Chem 1886;10:391–400.
    1. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.10.1016/0003-2697(76)90527-3
    1. Escalante-Gómez C, Zeledón-Sánchez F, Ulate-Montero G. Proteinuria, fisiología y fisiopatología aplicada. Acta Médica Costarricense 2007;49:83–9.
    1. World Medical Association WMA - The World Medical Association-WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. Available: [Accessed 15 Apr 2019].
    1. Ferenbach DA, Bonventre JV. Acute kidney injury and chronic kidney disease: from the laboratory to the clinic. Nephrol Ther 2016;12 (Suppl 1):S41–8.10.1016/j.nephro.2016.02.005
    1. Le Clef N, Verhulst A, D'Haese PC, et al. . Unilateral renal ischemia-reperfusion as a robust model for acute to chronic kidney injury in mice. PLoS One 2016;11:e015215310.1371/journal.pone.0152153
    1. World Health Organization Research for international tobacco control. who report on the global tobacco epidemic. The MPOWER package 2008.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner