Serum Copeptin Çocukluk Çağı İdrar Yolu Enfeksiyonlarının Tanısında Kullanılabilir mi?

Öz

Amaç: Üriner sistem enfeksiyonu (ÜSE)’nin erken teşhis edilmesi kısa ve uzun dönem etkileri azaltmak için önemlidir. Bu amaçla etkili biyobelirteçlere ihtiyaç vardır. Bu çalışmada, copeptinin diğer inflamatuvar belirteçlere göre ÜSE tanısında ve alt-üst ÜSE ayırımında rolünü değerlendirmeyi amaçladık. Yöntem: ÜSE tanısı, tipik klinik semptomlar ve pozitif idrar kültürüne dayanılarak konuldu. Kontrol grubu enfeksiyon bulgusu olmayan sağlıklı çocuklardan oluşturuldu. Hastaların tam kan sayımı, CRP, sedimentasyon, serum IL-6, NGAL ve copeptin düzeyleri değerlendirildi. Bulgular: Çalışmaya 41'er tane ÜSE ve sağlıklı birey dahil edildi. Hastaların yaşları 5 (0.8-15) yıl olup, %65.9’u kadın idi. ÜSE’si olanlarda WBC (p<0.001) ve NGAL (p=0.031) yanında copeptin (147.9(60.8-361.9) vs. 69.7(24.2-303) ng/ml, p<0.001) seviyeleri anlamlı oranda yüksekti. Copeptinin 81.8 ng/ml cut-off değeri ÜSE'ye işaret etmekteydi (sensitivite %80.4, spesifite %60.5, p<0.001). ÜSE grubunun 10 tanesi üst, 31 tanesi de alt ÜSE tanısına sahipti. Üst ÜSE hastalarında WBC (p=0.019), CRP (p<0.001), sedimentasyon (p<0.001) ve NGAL (p=0.046) seviyeleri anlamlı oranda yüksekti. Copeptin üst ve alt ÜSE grupları arasında farklılık göstermemekteydi. Copeptin IL-6 ve NGAL ile ilişkili bulundu (sırasıyla r²=0.23, p=0.002; r²=0.89, p<0.001). Sonuç: Copeptin çocukluk çağı ÜSE tanısında kullanılabilecek faydalı bir biyobelirteçtir, ancak üst ve alt ÜSE ayrımdaki rolünü değerlendirmek için daha kapsamlı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Copeptin
• NGAL
• IL-6
• İdrar Yolu Enfeksiyonu
• Çocuk

Could Serum Copeptin Be Used for Diagnosing Urinary Tract Infections in Children?

Öz

Objective: Early diagnosis of urinary tract infection (UTI) is important to reduce short- and long-term complications. To this end, effective biomarkers are needed. Our aim was to evaluate the role of copeptin in the diagnosis of UTI and in distinguishing upper from lower UTI compared to other inflammatory markers. Methods: The diagnosis of UTI was based on the presence of typical clinical symptoms and a positive urine culture. The control group was formed by healthy children without signs or symptoms of infection. Complete blood count, CRP, ESR, serum IL -6, NGAL and copeptin were evaluated. Results: The study group included 41 patients with UTI and 41 healthy controls. The patients were 5 (0.8-15) years old and 65.9% of them were female. In the patients with UTI, in addition to total WBC (p<0.001) and NGAL (p=0.031), copeptin was also increased (147.9(60.8-361.9) vs. 69.7(24.2-303) ng/ml, p<0.001). Copeptin could diagnose UTI at a cut-off value of 81.8 ng/ml (p<0.001, sensitivity 80.4%, specificity 60.5%). Within the UTI group, 10 had upper UTI and 31 had lower UTI. In the upper UTI group WBC (p=0.019), CRP (p<0.001), ESR (p<0.001) and NGAL (p=0.046) were higher. Copeptin did not differ between upper and lower UTI groups (p=0.82). Copeptin correlated with IL -6 and NGAL (r²=0.23, p=0.002; r²=0.89, p<0.001, respectively). Conclusion: Copeptin is a useful biomarker to use in the diagnosis of childhood UTI, but more comprehensive studies are needed to evaluate its role in distinguishing upper from lower UTI.

Anahtar Kelimeler

• Copeptin
• UTI
• NGAL
• IL-6
• Child

Kaynakça

1. Elder JS. Urinary Tract Infections. In: Kliegman RM, Stanton BF, St Gemell JW, Schor NF. eds. Nelson Textbook of Pediatrics 20th ed. Philadelphia, PA: Elsevier Saunders 2016:2556-2562
2. Mattoo TK, Mathews R, Gupta IR. Vesicoureteral Reflux and Renal Scarring in Children. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL, eds. Pediatric Nephrology 7th ed. Springer-Verlag Berlin Heidelberg 2016:1715-1748 https://doi.org/10.1007/978-3-662-43596-0_50
3. Bek K, Akman S, Bilge I, Topaloglu R, Caliskan S, Peru H, et al. Chronic kidney disease in children in Turkey. Pediatr Nephrol 2009;24(4):797-806 https://doi.org/10.1007/s00467-008-0998-4
4. Kim BK, Yim HE, Yoo KH. Plasma neutrophil gelatinase-associated lipocalin: a marker of acute pyelonephritis in children. Pediatr Nephrol 2016; https://doi.org/10.1007/s00467-016-3518-y
5. Mahyar A, Ayazi P, Maleki MR, Daneshi-Kohan MM, Sarokhani HR, Hashemi HJ, et al. Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children. Korean J Pediatr 2013;56(5): 218-223 https://doi.org/10.3345/kjp.2013.56.5.218
6. Han SY, Lee IR, Park SJ, Kim JH, Shin JI. Usefulness of neutrophil-lymphocyteratio in young children with febrile urinary tract infection. Korean J Pediatr 2016; 59(3): 139-144 https://doi.org/10.3345/kjp.2016.59.3.139
7. Katan M, Morgenthaler N, Widmer I, Puder JJ, König C, Müller B, et al. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuroendocrinology Letters 2008;29(3):341-346
8. Balanescu S, Kopp P, Gaskill MB, Morgenthaler NG, Schindler C, Rutishauser J. Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and hyperosmolar States. J Clin Endocrinol Metab. 2011;96:1046-52 https://doi.org/10.1210/jc.2010-2499

9. Christ-Crain M. Vasopressin and Copeptin in health and disease. Reviews in Endocrine and Metabolic Disorders 2019;20:283-294 https://doi.org/10.1007/s11154-019-09509-9
10. Morgenthaler NG, Müller B, Struck J, Bergmann A, Redl H, Christ-Crain M. Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock. Shock 2007;28(2):219-26 https://doi.org/10.1097/SHK.0b013e318033e5da
11. Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clinical Chemistry 2006;52(1):112-119 https://doi.org/10.1373/clinchem.2005.060038
12. Khan SQ, Dhillon OS, O'Brien RJ, Struck J, Quinn PA, Morgenthaler NG. C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study. Circulation 2007; 115: 2103-10 https://doi.org/10.1161/CIRCULATIONAHA.106.685503
13. Müller B, Morgenthaler N, Stolz D, P Schuetz, C Müller, R Bingisser, et al. Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections. Eur J Clin Invest 2007; 37: 145-52 https://doi.org/10.1111/j.1365-2362.2007.01762.x
14. Masajtis-Zagajewska A, Kurnatowska I, Wajdlich M, Nowicki M. Utility of copeptin and Standard inflammatory markers in the diagnostics of upper and lower urinary tract infections. BMC Urology 2015;15:67 https://doi.org/10.1186/s12894-015-0061-2
15. Stein R, Dogan HS, Hoebeke P, Kocvara R, Nijman RJ, Radmayr C, et al. Urinary Tract Infections in Children: EAU/ESPU Guidelines. Eur Urol 2015;67(3):546-558. https://doi.org/10.1016/j.eururo.2014.11.007
16. de Kruif MD, Lemaire LC, Giebelen IA, Struck J, Morgenthaler NG, Papassotiriou J, et al. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med 2008;34:518-522 https://doi.org/10.1007/s00134-007-0955-x
17. Bhandari SS, Loke I, Davies JE, Squire IB, Struck J, Ng LL. Gender and renal function influence plasma levels of copeptin in healthy individuals. Clin Sci (Lond) 2009;116:257-263 https://doi.org/10.1042/CS20080140
18. Fluri F, Morgenthaler N, Mueller B, Christ-Crain M, Katan M. Copeptin, procalcitonin and routine inflammatory markers-predictors of infection after stroke. PLoS One 2012;7: doi: 10.1371/journal.pone.0048309 https://doi.org/10.1371/journal.pone.0048309
19. Kageyama K, Hanada K, Iwasaki Y, Sakihara S, Nigawara T, Kasckow J, Suda T. Pituitary adenylate cyclase-activating polypeptide stimulates corticotropin-releasing factor, vasopressin and interleukin-6 gene transcription in hypothalamic 4B cells. J Endocrinol 2007;195:199-211 https://doi.org/10.1677/JOE-07-0125
20. Sim JH, Yim HE, Choi BM, Lee JH, Yoo KH. Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections. Pediatr Res. 2015;78(1):48-55. doi: 10.1038/pr.2015.59 https://doi.org/10.1038/pr.2015.59
21. Williams DM. Clinical pharmacology of corticosteroids. Respir Care 2018;63:655-70
22. Volpi S, Rabadan-Diehl C, Aguilera G. Vasopressinergic regulation of the hypothalamic pituitary adrenal axis and stress adaptation. Stress 2004;7:75-83
23. Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, et al. Incremental value of Copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol 2009;54:60-68 https://doi.org/10.1016/j.jacc.2009.01.076