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Published in: BMC Urology 1/2015

Open Access 01-12-2015 | Research article

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms

Authors: Kiren Gill, Harry Horsley, Anthony S Kupelian, Gianluca Baio, Maria De Iorio, Sanchutha Sathiananamoorthy, Rajvinder Khasriya, Jennifer L Rohn, Scott S Wildman, James Malone-Lee

Published in: BMC Urology | Issue 1/2015

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Abstract

Background

Adenosine-5′-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice.

Methods

A prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated.

Results

75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc μl-1 (n = 120) and pyuria ≥10 wbc μl-1 (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc μl-1 and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ≤ -20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing.

Conclusions

Urinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker.
Literature
1.
go back to reference Coyne KS, Sexton CC, Thompson CL, Milsom I, Irwin D, Kopp ZS, et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. B J UInt. 2009;104(3):352–60. Coyne KS, Sexton CC, Thompson CL, Milsom I, Irwin D, Kopp ZS, et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. B J UInt. 2009;104(3):352–60.
2.
go back to reference Staskin D, Kelleher C, Bosch R, Cotterill N, Emmanuel A, Yoshida M, et al. Initial Assessment of Urinary and Faecal Incontinence in Adult Male and Female Patients. In: Abrams P, Cardozo L, Khoury S, Wein A, editors. 4th International Conusltation on Incontinence. International Conusltation on Incontinence, vol. 1. Paris: Health Publications Ltd; 2009. p. 333–62. Staskin D, Kelleher C, Bosch R, Cotterill N, Emmanuel A, Yoshida M, et al. Initial Assessment of Urinary and Faecal Incontinence in Adult Male and Female Patients. In: Abrams P, Cardozo L, Khoury S, Wein A, editors. 4th International Conusltation on Incontinence. International Conusltation on Incontinence, vol. 1. Paris: Health Publications Ltd; 2009. p. 333–62.
3.
go back to reference Khasriya R, Khan S, Lunawat R, Bishara S, Bignal J, Malone-Lee M, et al. The Inadequacy of Urinary Dipstick and Microscopy as Surrogate Markers of Urinary Tract Infection in Urological Outpatients With Lower Urinary Tract Symptoms Without Acute Frequency and Dysuria. J Urol. 2010;183(5):1843–7.CrossRefPubMed Khasriya R, Khan S, Lunawat R, Bishara S, Bignal J, Malone-Lee M, et al. The Inadequacy of Urinary Dipstick and Microscopy as Surrogate Markers of Urinary Tract Infection in Urological Outpatients With Lower Urinary Tract Symptoms Without Acute Frequency and Dysuria. J Urol. 2010;183(5):1843–7.CrossRefPubMed
4.
go back to reference Deville WL, Yzermans JC, van Duijn NP, Bezemer PD, van der Windt DA, Bouter LM. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urol. 2004;4:4.CrossRefPubMedPubMedCentral Deville WL, Yzermans JC, van Duijn NP, Bezemer PD, van der Windt DA, Bouter LM. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urol. 2004;4:4.CrossRefPubMedPubMedCentral
5.
go back to reference Gorelick MH, Shaw KN. Screening tests for urinary tract infection in children: A meta-analysis. Pediatrics. 1999;104(5):e54.CrossRefPubMed Gorelick MH, Shaw KN. Screening tests for urinary tract infection in children: A meta-analysis. Pediatrics. 1999;104(5):e54.CrossRefPubMed
6.
go back to reference Stamm WE, Counts GW, Running KR, Fihn S, Turck M, Holmes KK. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med. 1982;307(8):463–8.CrossRefPubMed Stamm WE, Counts GW, Running KR, Fihn S, Turck M, Holmes KK. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med. 1982;307(8):463–8.CrossRefPubMed
7.
go back to reference Kass EH. Bacteriuria and the diagnosis of infection in the urinary tract. Arch Intern Med. 1957;100:709–14.CrossRef Kass EH. Bacteriuria and the diagnosis of infection in the urinary tract. Arch Intern Med. 1957;100:709–14.CrossRef
8.
go back to reference Siegman-Igra Y. The significance of urine culture with mixed flora. Curr Opin Nephrol Hypertens. 1994;3(6):656–9. PubMed PMID: 7881993. Epub 1994/11/01. eng.CrossRefPubMed Siegman-Igra Y. The significance of urine culture with mixed flora. Curr Opin Nephrol Hypertens. 1994;3(6):656–9. PubMed PMID: 7881993. Epub 1994/11/01. eng.CrossRefPubMed
9.
go back to reference Hurlbut 3rd TA, Littenberg B. The diagnostic accuracy of rapid dipstick tests to predict urinary tract infection. Am J Clin Pathol. 1991;96(5):582–8. PubMed PMID: 1951183. Epub 1991/11/01. eng.CrossRefPubMed Hurlbut 3rd TA, Littenberg B. The diagnostic accuracy of rapid dipstick tests to predict urinary tract infection. Am J Clin Pathol. 1991;96(5):582–8. PubMed PMID: 1951183. Epub 1991/11/01. eng.CrossRefPubMed
10.
go back to reference Burnstock G. Therapeutic potential of purinergic signalling for diseases of the urinary tract. BJU Int. 2011;107(2):192–204. PubMed PMID: 21208364. Epub 2011/01/07. eng.CrossRefPubMed Burnstock G. Therapeutic potential of purinergic signalling for diseases of the urinary tract. BJU Int. 2011;107(2):192–204. PubMed PMID: 21208364. Epub 2011/01/07. eng.CrossRefPubMed
11.
go back to reference Van der Wijk T, De Jonge HR, Tilly BC. Osmotic cell swelling-induced ATP release mediates the activation of extracellular signal-regulated protein kinase (Erk)-1/2 but not the activation of osmo-sensitive anion channels. Biochem J. 1999;343(Pt 3):579–86. PubMed PMID: 10527936. Pubmed Central PMCID: 1220589. Epub 1999/10/21. eng.CrossRefPubMedPubMedCentral Van der Wijk T, De Jonge HR, Tilly BC. Osmotic cell swelling-induced ATP release mediates the activation of extracellular signal-regulated protein kinase (Erk)-1/2 but not the activation of osmo-sensitive anion channels. Biochem J. 1999;343(Pt 3):579–86. PubMed PMID: 10527936. Pubmed Central PMCID: 1220589. Epub 1999/10/21. eng.CrossRefPubMedPubMedCentral
12.
go back to reference van der Weyden L, Conigrave AD, Morris MB. Signal transduction and white cell maturation via extracellular ATP and the P2Y11 receptor. Immunol Cell Biol. 2000;78(4):369–74. PubMed PMID: 10947861. Epub 2000/08/18. eng.CrossRefPubMed van der Weyden L, Conigrave AD, Morris MB. Signal transduction and white cell maturation via extracellular ATP and the P2Y11 receptor. Immunol Cell Biol. 2000;78(4):369–74. PubMed PMID: 10947861. Epub 2000/08/18. eng.CrossRefPubMed
13.
go back to reference Lundin A, Hallander H, Kallner A, Lundin UK, Osterberg E. Bacteriuria testing by the ATP method as an integral part in the diagnosis and therapy of urinary tract infection (UTI). J Biolumin Chemilumin. 1989;4(1):381–9. PubMed PMID: 2801224, Epub 1989/07/01. eng.CrossRefPubMed Lundin A, Hallander H, Kallner A, Lundin UK, Osterberg E. Bacteriuria testing by the ATP method as an integral part in the diagnosis and therapy of urinary tract infection (UTI). J Biolumin Chemilumin. 1989;4(1):381–9. PubMed PMID: 2801224, Epub 1989/07/01. eng.CrossRefPubMed
14.
go back to reference Save S, Persson K. Extracellular ATP and P2Y receptor activation induce a proinflammatory host response in the human urinary tract. Infect Immun. 2010;78(8):3609–15.CrossRefPubMedPubMedCentral Save S, Persson K. Extracellular ATP and P2Y receptor activation induce a proinflammatory host response in the human urinary tract. Infect Immun. 2010;78(8):3609–15.CrossRefPubMedPubMedCentral
15.
go back to reference Hanberger H, Nilsson LE, Kihlstrom E, Maller R. Postantibiotic effect of beta-lactam antibiotics on Escherichia coli evaluated by bioluminescence assay of bacterial ATP. Antimicrob Agents Chemother. 1990;34(1):102–6. PubMed PMID: 2183707, Pubmed Central PMCID: 171528. Epub 1990/01/01. eng.CrossRefPubMedPubMedCentral Hanberger H, Nilsson LE, Kihlstrom E, Maller R. Postantibiotic effect of beta-lactam antibiotics on Escherichia coli evaluated by bioluminescence assay of bacterial ATP. Antimicrob Agents Chemother. 1990;34(1):102–6. PubMed PMID: 2183707, Pubmed Central PMCID: 171528. Epub 1990/01/01. eng.CrossRefPubMedPubMedCentral
16.
go back to reference Poulis JA, de Pijper M, Mossel DA, Dekkers PP. Assessment of cleaning and disinfection in the food industry with the rapid ATP-bioluminescence technique combined with the tissue fluid contamination test and a conventional microbiological method. Int J Food Microbiol. 1993;20(2):109–16. PubMed PMID: 8268054. Epub 1993/11/01. eng.CrossRefPubMed Poulis JA, de Pijper M, Mossel DA, Dekkers PP. Assessment of cleaning and disinfection in the food industry with the rapid ATP-bioluminescence technique combined with the tissue fluid contamination test and a conventional microbiological method. Int J Food Microbiol. 1993;20(2):109–16. PubMed PMID: 8268054. Epub 1993/11/01. eng.CrossRefPubMed
17.
go back to reference Meers PD, Chow CK. Bacteriostatic and bactericidal actions of boric acid against bacteria and fungi commonly found in urine. J Clin Pathol. 1990;43(6):484–7.CrossRefPubMedPubMedCentral Meers PD, Chow CK. Bacteriostatic and bactericidal actions of boric acid against bacteria and fungi commonly found in urine. J Clin Pathol. 1990;43(6):484–7.CrossRefPubMedPubMedCentral
18.
go back to reference Khan S, Chandhyoke N, Bishara S, Mahmood W, Khasriya RK, Lunawat R, et al. The Preservation of Pyuria in Urine Samples with Boric Acid. Int Urogynecol J. 2009;20:S132–S3. Khan S, Chandhyoke N, Bishara S, Mahmood W, Khasriya RK, Lunawat R, et al. The Preservation of Pyuria in Urine Samples with Boric Acid. Int Urogynecol J. 2009;20:S132–S3.
19.
go back to reference Avery K, Donovan J, Peters TJ, Shaw C, Gotoh M, Abrams P. ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol Urodyn. 2004;23(4):322–30.CrossRefPubMed Avery K, Donovan J, Peters TJ, Shaw C, Gotoh M, Abrams P. ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol Urodyn. 2004;23(4):322–30.CrossRefPubMed
20.
go back to reference Heuer RJ. Center for the Study of Intelligence (U.S.). Psychology of intelligence analysis. New York: Novinka Books; 2006. xii, 216 p. p. Heuer RJ. Center for the Study of Intelligence (U.S.). Psychology of intelligence analysis. New York: Novinka Books; 2006. xii, 216 p. p.
21.
go back to reference Al Buheissi S, Khasriya R, Maraj BH, Malone-Lee J. A simple validated scale to measure urgency. J Urol. 2008;179(3):1000–5.CrossRefPubMed Al Buheissi S, Khasriya R, Maraj BH, Malone-Lee J. A simple validated scale to measure urgency. J Urol. 2008;179(3):1000–5.CrossRefPubMed
22.
go back to reference Gill K, Kupelian A, Brackenridge L, Horsley H, Sathiananthamoorthy S, Malone-Lee J. Surprising symptoms indicating urinary tract infection. International Continence Society Meeting 2011. Glasgow: International Continence Society; 2011. Gill K, Kupelian A, Brackenridge L, Horsley H, Sathiananthamoorthy S, Malone-Lee J. Surprising symptoms indicating urinary tract infection. International Continence Society Meeting 2011. Glasgow: International Continence Society; 2011.
23.
go back to reference Kupelian A, Chaliha C, Gill K, Brackenridge L, Horsley H, Malone-Lee J. Pain symptoms as part of the OAB complex. Int Urogynecol J. 2009;22 Suppl 1:189–90. Kupelian A, Chaliha C, Gill K, Brackenridge L, Horsley H, Malone-Lee J. Pain symptoms as part of the OAB complex. Int Urogynecol J. 2009;22 Suppl 1:189–90.
24.
go back to reference Khasriya R, Sathiananthamoorthy S, Ismail S, Kelsey M, Wilson M, Rohn JL, et al. Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol. 2013;51(7):2054–62.CrossRefPubMedPubMedCentral Khasriya R, Sathiananthamoorthy S, Ismail S, Kelsey M, Wilson M, Rohn JL, et al. Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol. 2013;51(7):2054–62.CrossRefPubMedPubMedCentral
25.
go back to reference McGinley M, Wong LL, McBride JH, Rodgerson DO. Comparison of various methods for the enumeration of blood cells in urine. J Clin Lab Anal. 1992;6(6):359–61.CrossRefPubMed McGinley M, Wong LL, McBride JH, Rodgerson DO. Comparison of various methods for the enumeration of blood cells in urine. J Clin Lab Anal. 1992;6(6):359–61.CrossRefPubMed
26.
go back to reference Kupelian AS, Horsley H, Khasriya R, Amussah RT, Badiani R, Courtney AM, et al. Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: results from a clinical and laboratory evaluation. BJU International. 2013;112(2):231–8.CrossRefPubMed Kupelian AS, Horsley H, Khasriya R, Amussah RT, Badiani R, Courtney AM, et al. Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: results from a clinical and laboratory evaluation. BJU International. 2013;112(2):231–8.CrossRefPubMed
27.
go back to reference Osterberg E, Hallander HO, Kallner A, Lundin A, Aberg H. Evaluation of the adenosine triphosphate test in the diagnosis of urinary tract infection. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 1991. Feb;10(2):70-3. PubMed PMID: 1864277. Osterberg E, Hallander HO, Kallner A, Lundin A, Aberg H. Evaluation of the adenosine triphosphate test in the diagnosis of urinary tract infection. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 1991. Feb;10(2):70-3. PubMed PMID: 1864277.
28.
go back to reference Crawford ED, Rove KO, Trabulsi EJ, Qian J, Drewnowska KP, Kaminetsky JC, et al. Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases. J Urol. 2012;188(5):1726–31. PubMed PMID: 22998901.CrossRefPubMed Crawford ED, Rove KO, Trabulsi EJ, Qian J, Drewnowska KP, Kaminetsky JC, et al. Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases. J Urol. 2012;188(5):1726–31. PubMed PMID: 22998901.CrossRefPubMed
29.
go back to reference Burnstock G, Cocks T, Kasakov L, Wong HK. Direct evidence for ATP release from non-adrenergic, non-cholinergic (“purinergic”) nerves in the guinea-pig taenia coli and bladder. Eur J Pharmacol. 1978;49(2):145–9. PubMed PMID: 658131. Epub 1978/05/15. eng.CrossRefPubMed Burnstock G, Cocks T, Kasakov L, Wong HK. Direct evidence for ATP release from non-adrenergic, non-cholinergic (“purinergic”) nerves in the guinea-pig taenia coli and bladder. Eur J Pharmacol. 1978;49(2):145–9. PubMed PMID: 658131. Epub 1978/05/15. eng.CrossRefPubMed
30.
go back to reference Bayliss M, Wu C, Newgreen D, Mundy AR, Fry CH. A quantitative study of atropine-resistant contractile responses in human detrusor smooth muscle, from stable, unstable and obstructed bladders. J Urol. 1999;162(5):1833–9. PubMed PMID: 10524944.CrossRefPubMed Bayliss M, Wu C, Newgreen D, Mundy AR, Fry CH. A quantitative study of atropine-resistant contractile responses in human detrusor smooth muscle, from stable, unstable and obstructed bladders. J Urol. 1999;162(5):1833–9. PubMed PMID: 10524944.CrossRefPubMed
Metadata
Title
Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms
Authors
Kiren Gill
Harry Horsley
Anthony S Kupelian
Gianluca Baio
Maria De Iorio
Sanchutha Sathiananamoorthy
Rajvinder Khasriya
Jennifer L Rohn
Scott S Wildman
James Malone-Lee
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2015
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-015-0001-1

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