Publication: Sırs/ sepsis ve febril nötropeni tanılı pediatrik hastalarda supar'ın (soluble urokinase plasmınogen activator receptor) diagnostik ve prognostik değerinin c-reaktif protein ve prokalsitonin ile karşılaştırılması
Abstract
SIRS, Sepsis ve Febril Nötropeni Tanılı Pediatrik Hastalarda suPAR’ın Diagnostik ve Prognostik Değerinin CRP ve Prokalsitonin ile Karşılaştırılması Giriş: suPAR çeşitli immünolojik hücrelerde bulunan urokinaz plazminojen aktivatör reseptörünün (uPAR) çözülebilir formudur. suPAR’ın SIRS ve sepsis tanılı hastalarda hastalık ciddiyeti ve mortalite riskini öngörmede bir belirteç olarak kullanılabileceği düşünülmektedir. Ancak suPAR’ın SIRS, sepsis ve febril nötropeni tanılı çocuk hastalarda tanısal ve prognostik değeri çalışılmamıştır. Bu çalışmanın amacı suPAR’ın SIRS/ sepsis ve febril nötropeni tanıları olan çocuk hastalarda tanısal ve prognostik değerinin belirlenmesi; bu hasta gruplarında CRP ve PCT ile karşılaştırılmasıdır. Yöntem: Febril nötropeni (FN) tanılı 29 çocuk hasta, SIRS/ sepsis tanılı 27 çocuk hasta ve herhangi bir aktif enfeksiyon veya immün yetmezlik öyküsü olmayan 27 çocuk kontrol olgusu dahil edilerek prospektif bir çalışma yapıldı. Hastalardan serum örnekleri hastaneye ilk başvuru günü içerisinde ve yatışlarının 4 – 7 günleri arasında alındı, kontrol grubundan ise sadece bir kez kan örneği alındı. suPAR ölçümleri ELİSA yöntemi ile yapıldı. Aynı serum örneklerinden CRP ve PCT ölçümleri sırası ile immün nefelometri ve floresan immünoassay yöntemleri ile çalışıldı. Bulgular: İlk başvuru gününde alınan serum örneklerindeki ortanca suPAR düzeyleri FN, SIRS/ sepsis ve kontrol grupları için sırası ile 2,08 (0,93 – 9,42), 10,06 (2,7 – 57,46) ve 2,22 (1,08 – 5,13) ng/ mL saptandı. Ortanca değerler karşılaştırıldığında FN ve kontrol grubu arasında anlamlı farklılık saptanmazken SIRS/ sepsis grubunun değerleri diğer gruplar ile karşılaştırıldığında istatistiksel olarak anlamlı düzeyde yüksek bulundu (p<0,01). Hem FN hem de SIRS/ sepsis gruplarında serum suPAR düzeyleri kaybedilen hastalarda hayatta kalanlara oranla önemli ölçüde yüksek bulundu (p<0,05). FN grubu için suPAR’ın receiver operating characteristics curve altında kalan alanı (AUCROC) 0,546 saptandı; bu sebeple ideal kesme noktası, duyarlılık, özgüllük, negatif kestirim değeri (NKD) ve pozitif kestirim değeri (PKD) gibi değerlerler elde edilemedi ancak SIRS/ sepsis 6 grubunda; suPAR için AUCROC , ideal kesme noktası, duyarlılık, özgüllük, NKD, PKD sırası ile 0,978, 3,8 ng/ mL, %96, %96, %96 ve %96 saptandı. FN grubu için PCT’nin AUCROC , ideal kesme noktası, duyarlılık, özgüllük, NKD, PKD sırası ile 0,961, 0,36 ng/ mL, %89, %96, %96 ve %89 saptanırken; SIRS/ sepsis grubunda, PCT için AUCROC , ideal kesme noktası, duyarlılık, özgüllük, NKD, PKD sırası ile 0,954, 0,35 ng/ mL, %89, %92, %92 ve %89 saptandı. FN grubu için CRP’nin AUCROC , ideal kesme noktası, duyarlılık, özgüllük, NKD, PKD sırası ile 0,972, 8,03 mg/ L, %93, %92, %93 ve %92 saptanırken; SIRS/ sepsis grubunda, CRP için AUCROC , ideal kesme noktası, duyarlılık, özgüllük, NKD, PKD sırası ile 0,985, 6,68 mg/ L, %96, %92, %93 ve %96 saptandı. Sonuç: Çalışmanın sonucunda suPAR’ın febril nötropenisi olan çocuk hastalarda tanı koymada faydalı olmadığı ancak SIRS,/ sepsis tanılı pediatrik hastalarda tanısal değeri olduğu gösterilmiştir. Bununla birlikte yüksek serum suPAR düzeylerinin hem febril nötropeni hem de SIRS/ sepsis tanılı hastalarda mortalite ile ilişkili olduğu ortaya konulmuştur. Anahtar sözcükler: suPAR, SIRS, sepsis, febril nötropeni, biyolojik belirteç.
The diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and Procalcitonin (PCT) in Children with Systemic Inflammatory Response Syndrome (SIRS)/ sepsis and febrile neutropenia Introduction: suPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR) expressed in various immunologically active cells. It has been suggested that suPAR can be used as a marker of disease severity and risk of mortality in patients with SIRS/ sepsis. However the diagnostic and the prognostic value of suPAR in children with SIRS/ sepsis and febrile neutropenia has not been studied before. The aim with the present study was to determine diagnostic and prognostic values of suPAR and to compare CRP and PCT in pediatric patients with SIRS/ sepsis and febrile neutropenia. Methods: In a prospective study cohort we enrolled 29 children with febrile neutropenia (FN), 27 children with SIRS/ sepsis and 27 control subjects without any infection and immune supressive condition. Blood samples were obtained on the day of admission and on the 4-7th day of the hospital stay, only one sample was obtained from the control group. suPAR was measured using a commercial solid-phase ELISA. Measurements of CRP and PCT were made from the same serum specimens by using Particle-Enhanced immunonepholometry and Fluorescence Immunoassay, respectively. Results: The median serum levels of suPAR, obtained in the first day of the admission, for the FN group, SIRS/ sepsis group and control group were 2.08 (0.93 – 9.42), 10.06 (2.7 - 57.46), and 2.22 (1.08 – 5.13) ng/ mL, respectively. The median serum levels in FN and control group showed no statiscally significant difference but serum levels in SIRS/ sepsis group was significantly higher than the control group (p<0.01). Serum suPAR levels were significantly higher in nonsurvivors compared to survivors in both FN and SIRS/ sepsis groups (p<0,05). In patients with FN, area under the receiever operating characteristics curve (AUCROC) of suPAR was 0,546; no optimum cut off point, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were 8 obtained but in SIRS/ sepsis group patients the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of suPAR, were 0.978, 3.8 ng/ mL, 96%, 96%, 96%, and 96%, respectively. In FN group patients the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of PCT, were 0.961, 0.36 ng/ mL, 89%, 96%, 96%, and 89%, respectively and in patients with SIRS/ sepsis, the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of PCT were 0.954, 0.35 ng/ mL, 89%, 92%, 92%, and 89%, respectively. In FN group patients the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of CRP, were 0.972, 8.03 mg/ L, 93%, 92%, 93%, and 92%, respectively and in patients with SIRS/ sepsis, the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of CRP were 0.985, 6,68 mg/ L, 96%, 92%, 93%, and 96%, respectively. Conclusions: We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia but has a diagnostic value in children with SIRS/ sepsis. Moreover persistent high serum suPAR level predicts mortality in both FN and SIRS/ sepsis patients. Key words: suPAR, SIRS, sepsis, febrile neutropenia, biomarker.
The diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and Procalcitonin (PCT) in Children with Systemic Inflammatory Response Syndrome (SIRS)/ sepsis and febrile neutropenia Introduction: suPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR) expressed in various immunologically active cells. It has been suggested that suPAR can be used as a marker of disease severity and risk of mortality in patients with SIRS/ sepsis. However the diagnostic and the prognostic value of suPAR in children with SIRS/ sepsis and febrile neutropenia has not been studied before. The aim with the present study was to determine diagnostic and prognostic values of suPAR and to compare CRP and PCT in pediatric patients with SIRS/ sepsis and febrile neutropenia. Methods: In a prospective study cohort we enrolled 29 children with febrile neutropenia (FN), 27 children with SIRS/ sepsis and 27 control subjects without any infection and immune supressive condition. Blood samples were obtained on the day of admission and on the 4-7th day of the hospital stay, only one sample was obtained from the control group. suPAR was measured using a commercial solid-phase ELISA. Measurements of CRP and PCT were made from the same serum specimens by using Particle-Enhanced immunonepholometry and Fluorescence Immunoassay, respectively. Results: The median serum levels of suPAR, obtained in the first day of the admission, for the FN group, SIRS/ sepsis group and control group were 2.08 (0.93 – 9.42), 10.06 (2.7 - 57.46), and 2.22 (1.08 – 5.13) ng/ mL, respectively. The median serum levels in FN and control group showed no statiscally significant difference but serum levels in SIRS/ sepsis group was significantly higher than the control group (p<0.01). Serum suPAR levels were significantly higher in nonsurvivors compared to survivors in both FN and SIRS/ sepsis groups (p<0,05). In patients with FN, area under the receiever operating characteristics curve (AUCROC) of suPAR was 0,546; no optimum cut off point, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were 8 obtained but in SIRS/ sepsis group patients the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of suPAR, were 0.978, 3.8 ng/ mL, 96%, 96%, 96%, and 96%, respectively. In FN group patients the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of PCT, were 0.961, 0.36 ng/ mL, 89%, 96%, 96%, and 89%, respectively and in patients with SIRS/ sepsis, the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of PCT were 0.954, 0.35 ng/ mL, 89%, 92%, 92%, and 89%, respectively. In FN group patients the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of CRP, were 0.972, 8.03 mg/ L, 93%, 92%, 93%, and 92%, respectively and in patients with SIRS/ sepsis, the AUCROC, optimum cut off point, sensitivity, specificity, NPV and PPV of CRP were 0.985, 6,68 mg/ L, 96%, 92%, 93%, and 96%, respectively. Conclusions: We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia but has a diagnostic value in children with SIRS/ sepsis. Moreover persistent high serum suPAR level predicts mortality in both FN and SIRS/ sepsis patients. Key words: suPAR, SIRS, sepsis, febrile neutropenia, biomarker.