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Photoacoustic detection of ammonia exhaled by individuals with chronic kidney disease

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Abstract

Ammonia (NH3) has been reported as a breath biomarker for chronic kidney disease (CKD) usually detected at concentrations greater than 0.25 parts per million by volume (ppmV). NH3 was detected in breath of individuals with CKD through gaseous photoacoustic spectroscopy (PAS). The efficiency of hemodialysis (HD) was demonstrated. Eight volunteers aged between 20 and 60 years and without previous respiratory disease were eligible, among which six were control volunteers (CV) and two volunteers with advanced CKD, named CKDV1 and CKDV2. The presence of CKD was confirmed by the calculation of creatinine clearance (CC) according to the Cockcroft–Gault equation. Before HD, the mean NH3 concentration exhaled by CKDV1 was 0.9 ± 0.1 ppmV and after HD was 0.20 ± 0.03 ppmV, which demonstrated an efficiency of 76% NH3 reduction in breath. The CKDV2 exhaled 1.27 ± 0.03 ppmV of NH3 pre-HD and 0.42 ± 0.08 ppmV post-HD, which resulted in efficiency of about 67%. It was not possible to quantify NH3 from CV, what led us to infer that all of them exhaled amounts below the detection limit, i.e., 0.20 ppmV. This assumption is underpinned by CC, whose values hovered at 90 ≤ CC ≤ 120 mL/ min, confirming normal renal function.

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Fig. 1
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taken from the highlighted blue points such as the maximum PA signal, the corresponding NH3 concentration, and wavenumber

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References

  1. (2013) Chapter 1: definition and classification of CKD. Kidney Int Suppl 3(1):19–62. https://doi.org/10.1038/kisup.2012.64

  2. Ammirati AL (2020) Chronic kidney disease. Rev Assoc Med Bras 66(suppl 1):s03–s09. https://doi.org/10.1590/1806-9282.66.s1.3

    Article  Google Scholar 

  3. Bello AK, Levin A, Tonelli M, Okpechi IG, Feehally J, Harris D, Jindal K, Salako BL, Rateb A, Osman MA, Qarni B, Saad S, Lunney M, Wiebe N, Ye F, Johnson DW (2017) Global Kidney Health Atlas: a report by the International Society of Nephrology on the current state of organization and structures for kidney care across the globe. Tech. rep., International Society of Nephrology, Brussels. https://www.theisn.org/initiatives/global-kidney-health-atlas/

  4. Bortolotto LA (2008) Hipertensão arterial e insuficiência renal crônica. Rev Bras Hipertens 15(3):152–155. http://departamentos.cardiol.br/dha/revista/15-3/09-hipertensao.pdf

  5. Chan MJ, Li YJ, Wu CC, Lee YC, Zan HW, Meng HF, Hsieh MH, Lai CS, Tian YC (2020) Breath ammonia is a useful biomarker predicting kidney function in chronic kidney disease patients. Biomedicines 8(11):468. https://doi.org/10.3390/biomedicines8110468

    Article  CAS  PubMed Central  Google Scholar 

  6. Chen W, Laiho S, Vaittinen O, Halonen L, Ortiz F, Forsblom C, Groop PH, Lehto M, Metsälä M (2016) Biochemical pathways of breath ammonia (NH3) generation in patients with end-stage renal disease undergoing hemodialysis. J Breath Res 10(3):036011. https://doi.org/10.1088/1752-7155/10/3/036011

    Article  CAS  PubMed  Google Scholar 

  7. Chen CC, Hsieh JC, Chao CH, Yang WS, Cheng HT, Chan CK, Lu CJ, Meng HF, Zan HW (2020) Correlation between breath ammonia and blood urea nitrogen levels in chronic kidney disease and dialysis patients. J Breath Res 14(3):036002. https://doi.org/10.1088/1752-7163/ab728b

    Article  CAS  PubMed  Google Scholar 

  8. Cockcroft DW, Gault H (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41. https://doi.org/10.1159/000180580

    Article  CAS  Google Scholar 

  9. Curl RF, Capasso F, Gmachl C, Kosterev AA, McManus B, Lewicki R, Pusharsky M, Wysocki G, Tittel FK (2010) Quantum cascade lasers in chemical physics. Chem Phys Lett 487(1–3):1–18. https://doi.org/10.1016/j.cplett.2009.12.073

    Article  CAS  Google Scholar 

  10. da Silva MG, Vargas H, Miklós A, Hess P (2004) Photoacoustic detection of ozone using a quantum cascade laser. Appl Phys B: Lasers Opt 78:677–680. https://doi.org/10.1007/s00340-004-1513-7

    Article  CAS  Google Scholar 

  11. de Souza Vieira EE, Bispo JAM, Silveira L, Fernandes AB (2017) Discrimination model applied to urinalysis of patients with diabetes and hypertension aiming at diagnosis of chronic kidney disease by Raman spectroscopy. Lasers Med Sci 32(7):1605–1613. https://doi.org/10.1007/s10103-017-2288-5

    Article  PubMed  Google Scholar 

  12. Davies SJ, Španěl P, Smith D (2014) Breath analysis of ammonia, volatile organic compounds and deuterated water vapor in chronic kidney disease and during dialysis. Bioanalysis 6(6):843–857. https://doi.org/10.4155/bio.14.26

    Article  CAS  PubMed  Google Scholar 

  13. Filho MDN, Burmeister JE, da Rosa Miltersteiner D, Campos BM, da Costa MG (2008) Estimativa da função renal pela fórmula de Cockcroft e Gault em pacientes com sobrepeso ou com obesidade. J Bras Nefrol 30(3):185–191. https://bjnephrology.org/wp-content/uploads/2019/08/jbn_v30n3a4.pdf

  14. Hibbard T, Crowley K, Kelly F, Ward F, Holian J, Watson A, Killard AJ (2013) Point of care monitoring of hemodialysis patients with a breath ammonia measurement device based on printed polyaniline nanoparticle sensors. Anal Chem 85(24):12158–12165. https://doi.org/10.1021/ac403472d

    Article  CAS  PubMed  Google Scholar 

  15. Hosten AO (1990) Clinical methods: the history, physical, and laboratory examinations, 3rd edn, Butterworths, chap 193, pp 874–878. https://www.ncbi.nlm.nih.gov/books/NBK305/

  16. Kim KH, Jahan SA, Kabir E (2012) A review of breath analysis for diagnosis of human health. TrAC Trends Anal Chem 33:1–8. https://doi.org/10.1016/j.trac.2011.09.013

    Article  CAS  Google Scholar 

  17. Koskinen V, Fonsen J, Kauppinen J, Kauppinen I (2006) Extremely sensitive trace gas analysis with modern photoacoustic spectroscopy. Vib Spectrosc 42(2):239–242. https://doi.org/10.1016/j.vibspec.2006.05.018

    Article  CAS  Google Scholar 

  18. Kosterev A, Wysocki G, Bakhirkin Y, So S, Lewicki R, Fraser M, Tittel F, Curl RF (2007) Application of quantum cascade lasers to trace gas analysis. Appl Phys B 90(2):165–176. https://doi.org/10.1007/s00340-007-2846-9

    Article  CAS  Google Scholar 

  19. Le HND, U-Thainual P, Kim DH (2015) Photoacoustic spectroscopy of gaseous biomarker in simulated breath. In: Gannot I (ed) Optical fibers and sensors for medical diagnostics and treatment applications XV. SPIE. https://doi.org/10.1117/12.2082703

  20. Li M, Weschler CJ, Bekö G, Wargocki P, Lucic G, Williams J (2020) Human ammonia emission rates under various indoor environmental conditions. Environ Sci Technol 54(9):5419–5428. https://doi.org/10.1021/acs.est.0c00094

    Article  CAS  PubMed  Google Scholar 

  21. Lourenço C, Turner C (2014) Breath analysis in disease diagnosis: methodological considerations and applications. Metabolites 4(2):465–498. https://doi.org/10.3390/metabo4020465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McCurdy MR, Bakhirkin Y, Wysocki G, Lewicki R, Tittel FK (2007) Recent advances of laser-spectroscopy-based techniques for applications in breath analysis. J Breath Res 1(1):014001. https://doi.org/10.1088/1752-7155/1/1/014001

    Article  CAS  PubMed  Google Scholar 

  23. Meinardi S, Jin KB, Barletta B, Blake DR, Vaziri ND (2013) Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease. Biochim Biophys Acta Gen Subj 1830(3):2531–2537. https://doi.org/10.1016/j.bbagen.2012.12.006

    Article  CAS  Google Scholar 

  24. Miklós A, Hess P, Bozóki Z (2001) Application of acoustic resonators in photoacoustic trace gas analysis and metrology. Rev Sci Instrum 72(4):1937–1955. https://doi.org/10.1063/1.1353198

    Article  CAS  Google Scholar 

  25. Narasimhan LR, Gordon W, Patel CKN (2001) Correlation of breath ammonia with blood urea nitrogen and creatine during hemodialysis. Proc Natl Acad Sci 98:4617–4621. https://doi.org/10.1073/pnas.071057598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Navas MJ, Jiménez AM, Asuero AG (2012) Human biomarkers in breath by photoacoustic spectroscopy. Clin Chim Acta 413(15–16):1171–1178. https://doi.org/10.1016/j.cca.2012.04.008

    Article  CAS  PubMed  Google Scholar 

  27. Obermeier J, Trefz P, Happ J, Schubert JK, Staude H, Fischer DC, Miekisch W (2017) Exhaled volatile substances mirror clinical conditions in pediatric chronic kidney disease. PLoS ONE 12(6):1–18. https://doi.org/10.1371/journal.pone.0178745

    Article  CAS  Google Scholar 

  28. Paschke KM, Mashir A, Dweik RA (2010) Clinical applications of breath testing. F1000 Med Rep. https://doi.org/10.3410/m2-56

    Article  PubMed  PubMed Central  Google Scholar 

  29. Patel SS, Molnar MZ, Tayek JA, Ix JH, Noori N, Benner D, Heymsfield S, Kopple JD, Kovesdy CP, Kalantar-Zadeh K (2012) Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature. J Cachexia Sarcopenia Muscle 4(1):19–29. https://doi.org/10.1007/s13539-012-0079-1

    Article  PubMed  PubMed Central  Google Scholar 

  30. Popa C, Dutu DCA, Cernat R, Matei C, Bratu AM, Banita S, Dumitras DC (2011) Ethylene and ammonia traces measurements from the patients’ breath with renal failure via LPAS method. Appl Phys B 105(3):669–674. https://doi.org/10.1007/s00340-011-4716-8

    Article  CAS  Google Scholar 

  31. Popa C, George BS, Patachia M, Dumitras D (2013) Spectroscopic study of ammonia at subjects with kidney failure: a case control study. Rev Roum Chim 58:779–784. http://revroum.lew.ro/wp-content/uploads/2013/9/Art%2007.pdf

  32. Popa C, Petrus M, Bratu AM (2015) Ammonia and ethylene biomarkers in the respiration of the people with schizophrenia using photoacoustic spectroscopy. J Biomed Opt 20(5):057006. https://doi.org/10.1117/1.jbo.20.5.057006

    Article  Google Scholar 

  33. Risby TH, Tittel FK (2010) Current status of mid infrared quantum and interband cascade lasers for clinical breath analysis. Opt Eng 49(11):111123. https://doi.org/10.1117/1.3498768

    Article  CAS  Google Scholar 

  34. Salazar JH (2014) Overview of urea and creatinine. Lab Med 45(1):e19–e20. https://doi.org/10.1309/lm920sbnzpjrjgut

    Article  Google Scholar 

  35. Schmidt FM, Vaittinen O, Metsälä M, Lehto M, Forsblom C, Groop PH, Halonen L (2013) Ammonia in breath and emitted from skin. J Breath Res 7(1):017109. https://doi.org/10.1088/1752-7155/7/1/017109

    Article  CAS  PubMed  Google Scholar 

  36. Schmohl A, Miklós A, Hess P (2001) Effects of adsorption–desorption processes on the response time and accuracy of photoacoustic detection of ammonia. Appl Opt 40(15):2571. https://doi.org/10.1364/ao.40.002571

    Article  CAS  PubMed  Google Scholar 

  37. Sigrist MW (2003) Trace gas monitoring by laser photoacoustic spectroscopy and related techniques (plenary). Rev Sci Instrum 74(1):486–490. https://doi.org/10.1063/1.1512697

    Article  CAS  Google Scholar 

  38. Solga SF, Mudalel ML, Spacek LA, Risby TH (2014) Fast and accurate exhaled breath ammonia measurement. J Vis Exp 88:1–6. https://doi.org/10.3791/51658

    Article  CAS  Google Scholar 

  39. Španěl P, Smith D (2018) What is the real utility of breath ammonia concentration measurements in medicine and physiology? J Breath Res 12(2):027102. https://doi.org/10.1088/1752-7163/aa907f

    Article  CAS  PubMed  Google Scholar 

  40. Tittel FK, Lewicki R, Dong L, Liu K, Risby TH, Solga S, Schwartz T (2012) Real time detection of exhaled human breath using quantum cascade laser-based sensor technology. In: Oraevsky AA, Wang LV (eds) Photons plus ultrasound: imaging and sensing 2012. SPIE. https://doi.org/10.1117/12.912273

  41. Turner C, Španěl P, Smith D (2006) A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS. Physiol Meas 27(4):321–337. https://doi.org/10.1088/0967-3334/27/4/001

    Article  PubMed  Google Scholar 

  42. Vaziri ND, Khazaeli M, Nunes ACF, Harley KT, Said H, Alipour O, Lau WL, Pahl MV (2016) Effects of end-stage renal disease and dialysis modalities on blood ammonia level. Hemodial Int 21(3):343–347. https://doi.org/10.1111/hdi.12510

    Article  PubMed  PubMed Central  Google Scholar 

  43. Wang JW, Xie H, Liang LR, Zhang W, Peng W, Yu QX (2011) Tunable fiber laser based photoacoustic spectrometer for breath ammonia analysis during hemodialysis. Laser Phys 22(1):327–330. https://doi.org/10.1134/s1054660x12010227

    Article  Google Scholar 

  44. Wojtas J, Tittel FK, Stacewicz T, Bielecki Z, Lewicki R, Mikolajczyk J, Nowakowski M, Szabra D, Stefanski P, Tarka J (2014) Cavity-enhanced absorption spectroscopy and photoacoustic spectroscopy for human breath analysis. Int J Thermophys 35(12):2215–2225. https://doi.org/10.1007/s10765-014-1586-4

    Article  CAS  Google Scholar 

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Acknowledgements

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior — Brazil (CAPES) — Finance Code 001. The authors thank the Brazilian funding agencies: Carlos Chagas Filho Research Support Foundation (FAPERJ), National Council for Scientific and Technological Development (CNPq), and the volunteers for their most valuable participation.

Funding

- FAPERJ and CNPq have supported this research through equipment acquisition and facilities maintenance.

- CAPES provided scholarships for L. G. Silva and S. C. E. Bueno.

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Authors and Affiliations

  1. Centro de Ciência e Tecnologia Laboratório de Ciências Físicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, Rio de Janeiro, 28013-602, Brazil

    Liana Genuncio Silva, Sâmylla Cristina Espécie Bueno, Marcelo Gomes da Silva, Leonardo Mota, Marcelo Silva Sthel & Maria Priscila Pessanha de Castro

  2. Clínica de Doenças Renais, Rua Saldanha Marinho, 444, Campos dos Goytacazes, Rio de Janeiro, 28013-022, Brazil

    Raymundo Martins Santiago Neto

  3. Faculdade de Medicina de Campos, Avenida Alberto Torres, 217, Campos dos Goytacazes, Rio de Janeiro, 28035-581, Brazil

    Valeska Mansur Kuba

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  1. Liana Genuncio Silva
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  2. Sâmylla Cristina Espécie Bueno
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  3. Marcelo Gomes da Silva
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Correspondence to Maria Priscila Pessanha de Castro.

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Silva, L.G., Bueno, S.C.E., da Silva, M.G. et al. Photoacoustic detection of ammonia exhaled by individuals with chronic kidney disease. Lasers Med Sci 37, 983–991 (2022). https://doi.org/10.1007/s10103-021-03342-w

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