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Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus

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Abstract

Background

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000.

Methods

Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10 weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20 UI/mL and on 24-h urine protein and serum complement (C3) levels.

Results

An interquartile range (IQR) increase of 18.12 μg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1 μg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels.

Conclusions

This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

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References

  1. Pinheiro SVB, Dias RF, Fabiano RCG, Araujo SA, Silva ACS (2018) Nefrite lúpica em pediatria. J Bras Nefrol 41:252–265

    PubMed  PubMed Central  Google Scholar 

  2. Campos LM, Omori CH, Lotito AP, Jesus AA, Porta G, Silva CA (2010) Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome? Lupus 19:1654–1658

    CAS  PubMed  Google Scholar 

  3. Silva CA, Bonfa E, Ostensen M (2010) Maintenance of fertility in patients with rheumatic diseases needing anti-inflammatory and immunosuppressive drugs. Arthritis Care Res (Hoboken) 62:1682–1690

    Google Scholar 

  4. Cavalcante EG, Guissa VR, Jesus AA, Campos LMA, Sallum AM, Aikawa NE, Silva CA (2011) Stevens-Johnson syndrome in a juvenile systemic lupus erythematosus patient. Lupus 20:1439–1441

    CAS  PubMed  Google Scholar 

  5. Cavalcante EG, Aikawa NE, Lozano RG, Lotito AP, Jesus AA, Silva CA (2011) Chronic polyarthritis as the first manifestation of juvenile systemic lupus erythematosus patients. Lupus 20:960–964

    CAS  PubMed  Google Scholar 

  6. Araujo DB, Borba EF, Silva CA, Campos LM, Pereira RM, Bonfa E, Shinjo SK (2012) Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus. Lupus 21:872–877

    CAS  PubMed  Google Scholar 

  7. Silva CA, Avcin T, Brunner HI, Silva CA, Aikawa NE, Pereira RM, Campos LM (2012) Taxonomy for systemic lupus erythematosus with onset before adulthood. Arthritis Care Res (Hoboken) 64:1787–1793

    Google Scholar 

  8. Silva CA, Aikawa NE, Pereira RM, Campos LM (2016) Management considerations for childhood-onset systemic lupus erythematosus patients and implications on therapy. Expert Rev Clin Immunol 12:301–313

    CAS  PubMed  Google Scholar 

  9. Levy DM, Kamphuis S (2012) Systemic lupus erythematosus in children and adolescents. Pediatr Clin N Am 59:345–364

    Google Scholar 

  10. Lewandowski LB, Schanberg LE, Thielman N, Phuti A, Kalla AA, Okpechi I, Nourse P, Gajjar P, Faller G, Ambaram P, Reuter H, Spittal G, Scott C (2017) Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa. Lupus 26:186–194

    CAS  PubMed  Google Scholar 

  11. Rocha MFB (2010) Lúpus eritematoso sistémico juvenil: aspectos clínicos e de prognóstico. Dissertation, Universidade do Porto

  12. Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E, Gladman DD, Urowitz M, Fortin PR, Petri M, Barr S, Gordon C, Bae SC, Isenberg D, Zoma A, Aranow C, Dooley MA, Nived O, Sturfelt G, Steinsson K, Alarcón G, Senécal JL, Zummer M, Hanly J, Ensworth S, Pope J, Edworthy S, Rahman A, Sibley J, El-Gabalawy H, McCarthy T, St Pierre Y, Clarke A, Ramsey-Goldman R (2006) Mortality in systemic lupus erythematosus. Arthritis Rheum 54:2550–2557

    CAS  PubMed  Google Scholar 

  13. Hahn BH, MA MM, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM, American College of Rheumatology (2012) American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 64:797–808

    Google Scholar 

  14. Ghirardello A, Villalta D, Morozzi G, Afeltra A, Galeazzi M, Gerli R, Mathieu A, Meroni PL, Pregnolato F, Migliorini P, Radice A, Riccieri V, Ruffatti A, Sebastiani GD, Sinico RA, Tincani A, Doria A, Forum Interdisciplinare per la Ricerca sulle Malattie Autoimmuni (FIRMA) study group (2011) Diagnostic accuracy of currently available anti-double-stranded DNA antibody assays. An Italian multicentre study. Clin Exp Rheumatol 29:50–56

    PubMed  Google Scholar 

  15. Smith EM, Yin P, Jorgensen AL, Beresford MW (2018) Clinical predictors of active LN development in children: evidence from the UK JSLE Cohort Study. Lupus 27:2020–2028

    CAS  PubMed  Google Scholar 

  16. Farhat SC, Silva CA, Orione MA, Campos LM, Sallum AM, Braga AL (2011) Air pollution in autoimmune rheumatic disease: a review. Autoimmun Rev 11:14–21

    CAS  PubMed  Google Scholar 

  17. Bernatsky S, Fournier M, Pineau CA, Clarke AE, Vinet E, Smargiassi A (2011) Associations between ambient fine particulate levels and disease activity in patients with systemic lupus erythematosus (SLE). Environ Health Perspect 119:45–49

    CAS  PubMed  Google Scholar 

  18. Vidotto JP, Pereira LA, Braga AL, Silva CA, Sallum AM, Campos LM, Martins LC, Farhat SC (2012) Atmospheric pollution: influence on hospital admissions in paediatric rheumatic diseases. Lupus 21:526–533

    CAS  PubMed  Google Scholar 

  19. Fernandes EC, Silva CA, Braga ALF, Sallum AME, Campos LMA, Farhat SCL (2015) Exposure to air pollutants increased disease activity in childhood-onset systemic lupus erythematosus patients. Arthritis Care Res 67:1609–1614

    CAS  Google Scholar 

  20. Alves AG, Giacomin MF, Braga AL, Sallum AME, Pereira LAA, Farhat LC, Strufaldi FL, Lichtenfels AJFC, Carvalho TS, Nakagawa NK, Silva CA, Farhat SCL (2018) Influence of air pollution on airway inflammation and disease activity in childhood-systemic lupus erythematosus. Clin Rheumatol 37:683–690

    PubMed  Google Scholar 

  21. Conde PG, Farhat LC, Braga ALF, Sallum AEM, Farhat SCL, Silva CA (2018) Are prematurity and environmental factors determinants for developing childhood-onset systemic lupus erythematosus? Mod Rheumatol 28:156–160

    PubMed  Google Scholar 

  22. Xu X, Wang G, Chen N, Lu T, Nie S, Xu G, Zhang P, Luo Y, Wang Y, Wang X, Schwartz J, Geng J, Hou FF (2016) Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol 27:3739–3746

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Omoloja A, Tyc VL (2015) Tobacco and the pediatric chronic kidney disease population. Pediatr Nephrol 30:235–243

    PubMed  Google Scholar 

  24. Lin S-Y, Hsu W-H, Lin C-L, Lin C-C, Lin C-H, Wang I-K, Hsu C-Y, Kao C-H (2018) Association of exposure to fine-particulate air pollution and acidic gases with incidence of nephrotic syndrome. Int J Environ Res Public Health 15:2860

    CAS  PubMed Central  Google Scholar 

  25. Hochberg MC (1977) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus (letter). Arthritis Rheum 40:1725

    Google Scholar 

  26. Novaes P, Saldiva PH, Matsuda M, Macchione M, Rangel MP, Kara-José N, Berra A (2010) The effects of chronic exposure to traffic derived air pollution on the ocular surface. Environ Res 110:372–374

    CAS  PubMed  Google Scholar 

  27. Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291

    PubMed  Google Scholar 

  28. Hanley JA, Negassa A, Edwardes MD, Forrester JE (2003) Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol 157:364–375

    PubMed  Google Scholar 

  29. World Health Organization. Occupational and Environmental Health Team (2006) WHO air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide: global update 2005: summary of risk assessment. World Health Organization

  30. Popov TA (2011) Human exhaled breath analysis. Ann Allergy Asthma Immunol 106:451–456

    CAS  PubMed  Google Scholar 

  31. Companhia Ambiental do Estado de São Paulo https://cetesb.sp.gov.br/ar/wp-content/uploads/sites/28/2019/05/Relat%C3%B3rio-de-Qualidade-do-Ar-2017.pdf. Accessed August 2019

  32. Carvalho VS, Freitas ED, Martins LD, Martins JA, Mazzoli CR, Andrade MF (2015) Air quality status and trends over the metropolitan area of São Paulo, Brazil as a result of emission control policies. Environ Sci Pol 47:68–79

    CAS  Google Scholar 

  33. de Oliveira AF, de Oliveira TF, Dias MF, Medeiros MHG, Di Mascio P, Veras M, Lemos M, Marcourakis T, Saldiva PHN, Loureiro APM (2018) Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from Sao Paulo, Brazil. Part Fibre Toxicol 15:40

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Reis MM, Guimarães MT, Braga AL, Martins LC, Pereira LA (2017) Air pollution and low birth weight in an industrialized city in Southeastern Brazil, 2003-2006. Rev Bras Epidemiol 20:189–199

    PubMed  Google Scholar 

  35. Jiang RT, Acevedo-Bolton V, Cheng KC, Klepeis NE, Ott WR, Hildermann LM (2011) Determination of response of real-time SidePak AM510 monitor to secondhand smoke, other common indoor aerosols, and outdoor aerosol. J Environ Monit 13:1695–1702

    CAS  PubMed  Google Scholar 

  36. Calderón-Garcidueñas L, Villareal-Calderon R, Valencia-Salazar G, Henríquez-Roldán C, Gutiérrez-Castrellon P, Coria-Jiménez R, Osnaya-Brizuela RL, Torres-Jardón R, Solt A, Reed W (2008) Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants. Inhal Toxicol 20:499–506

    PubMed  Google Scholar 

  37. Bowe B, Xie Y, Li T, Yan Y, Xian H, Al-Aly Z (2018) Particulate matter air pollution and the risk of incident CKD and progression to ESRD. J Am Soc Nephrol 29:218–230

    CAS  PubMed  Google Scholar 

  38. Liu D, Huang T, Chen N, Xu G, Zhang P, Luo Y, Wang Y, Lu T, Wang L, Xiong M, Geng J, Nie S (2018) The modern spectrum of biopsy-proven renal disease in Chinese diabetic patients: a retrospective descriptive study. Peer J 6:e4522

    PubMed  Google Scholar 

  39. Gandini M, Scarinzi C, Bande S, Berti G, Carná P, Ciancarella L, Costa G, Demaria M, Ghigo S, Piersanti A, Rowinski M, Spadea T, Stroscia M, Cadum E, LIFE MEDHISS collaborative group (2018) Long term effect of air pollution on incident hospital admissions: results from the Italian longitudinal study within LIFE MED HISS project. Environ Int 121:1087–1097

    CAS  PubMed  Google Scholar 

  40. Yang YR, Chen YM, Chen SY, Chan CC (2016) Associations between long-term particulate matter exposure and adult renal function in the Taipei Metropolis. Environ Health Perspect 125:602–607

    PubMed  PubMed Central  Google Scholar 

  41. Nemmar A, Karaca T, Beegam S, Yuvaraju P, Yasin J, Hamadi NK, Ali BH (2016) Prolonged pulmonary exposure to diesel exhaust particles exacerbates renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Cell Physiol Biochem 38:1703–1713

    CAS  PubMed  Google Scholar 

  42. McLaughlin MA (2014) WTC first responders are at higher risk for obstructive sleep apnea and PTSD. Medical Xpress https://medicalxpresscom/news/2014-03-wtc-higher-obstructive-apnea-ptsdhtml. Accessed 8 May 2019

  43. Angelini F, Pagano F, Bordin A, Milan M, Chimenti I, Peruzzi, Mariangela E (2017) The impact of environmental factors in influencing epigenetics related to oxidative states in the cardiovascular system. Oxi Med Cell Longev 1:1–18

    Google Scholar 

  44. Eom HJ, Choi J (2009) Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicol in Vitro 23:1326–1332

    CAS  PubMed  Google Scholar 

  45. Zhu J, Zhu LW, Yang JH, Xu W, Wang C, Li Z, Mau W, Lu D (2018) Proteomic analysis of human umbilical vein endothelial cells exposed to PM2.5. J Zhejiang Univ Sci B 19:458–470

    CAS  PubMed Central  Google Scholar 

  46. Nowling TK, Gilkeson GS (2011) Mechanisms of tissue injury in lupus nephritis. Arthritis Res Ther 13:250

    PubMed  PubMed Central  Google Scholar 

  47. Heidenreich U, Mayer G, Herold M, Klotz W, Stempfl Al-Jazrawi K, Lhotta K (2009) Sensitivity and specificity of autoantibody tests in the differential diagnosis of lupus nephritis. Lupus 18:1276–1280

    CAS  PubMed  Google Scholar 

  48. Wakiguchi H, Takei S, Kubota T, Miyazono A, Kawano Y (2017) Treatable renal disease in children with silent lupus nephritis detected by baseline biopsy: association with serum C3 levels. Clin Rheumatol 36:433–437

    PubMed  Google Scholar 

  49. Solorzano GTM, Silva MVM, Moreira SR, Nishida SK, Kirsztajn GM (2012) Urinary protein/creatinine ratio versus 24-hour proteinuria in the evaluation of lupus nephritis. J Bras Nefrol 34:64–67

    PubMed  Google Scholar 

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Funding

This study was supported by the São Paulo Research Support Foundation–FAPESP (grant no. 13/21508-2–SCLF), the National Council for Scientific and Technological Development–CNPq (grant nos. 302724/2011-7 and 472155/2012-1–CAS), the Federico Foundation (CAS), and the Research Support Group “Child and Adolescent Health”–NAP-CriAd, developed by Universidade de Sao Paulo–USP (CAS).

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Authors and Affiliations

  1. Pediatric Rheumatology Unit, Children’s Institute, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Maria Fernanda Giacomin Goulart, Andressa Guariento Ferreira Alves, Lúcia Maria de Arruda Campos, Clóvis Artur Almeida da Silva & Adriana Maluf Elias

  2. Pediatric Department, Hospital das Clınicas, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Maria Fernanda Giacomin Goulart, Andressa Guariento Ferreira Alves, Lúcia Maria de Arruda Campos, Clóvis Artur Almeida da Silva, Adriana Maluf Elias & Sylvia Costa Lima Farhat

  3. Laboratory of Experimental Air Pollution, LIM05, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Alfésio Luis Ferreira Braga, Luiz Alberto Amador Pereira, Ana Julia de Faria Coimbra Lichtenfels & Sylvia Costa Lima Farhat

  4. Environmental Exposure and Risk Assessment Group, Graduate Program in Collective Health, Universidade Catolica de Santos, Santos, Brazil

    Alfésio Luis Ferreira Braga & Luiz Alberto Amador Pereira

  5. Experimental Therapeutics Laboratory, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Ana Julia de Faria Coimbra Lichtenfels

  6. Rheumatology Department, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Clóvis Artur Almeida da Silva

  7. Environmental Epidemiology Study Group, Laboratory of Experimental Air Pollution, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Juliana Farhat, Alfésio Luis Ferreira Braga, Luiz Alberto Amador Pereira & Sylvia Costa Lima Farhat

Authors
  1. Maria Fernanda Giacomin Goulart
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  2. Andressa Guariento Ferreira Alves
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  3. Juliana Farhat
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  6. Ana Julia de Faria Coimbra Lichtenfels
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  7. Lúcia Maria de Arruda Campos
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  8. Clóvis Artur Almeida da Silva
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  9. Adriana Maluf Elias
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  10. Sylvia Costa Lima Farhat
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Corresponding author

Correspondence to Sylvia Costa Lima Farhat.

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The study was approved by the Local Ethics Committee of our University Hospital, and an age-appropriate written informed consent was obtained from all participants and their legal guardians.

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The authors declare that they have no conflicts of interest.

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Goulart, M.F.G., Alves, A.G.F., Farhat, J. et al. Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus. Pediatr Nephrol 35, 1247–1255 (2020). https://doi.org/10.1007/s00467-020-04517-3

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