Dr.Seher Açar, Çocukluk çağında alt ve üst üriner sistem enfeksiyonları tanısında kullanılan galektin-3'ün önemi, AİBÜ Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Tıpta Uzmanlık Tezi, Bolu, 2017Giriş:İdrar yolu enfeksiyonları (İYE); hekime en sık başvurulan bakteriyel hastalıklar arasındadır. Hastaların farklı klinik tablolarla başvurabilmeleri nedeniyle tanı ve tedavi gecikebilmektedir. Bu nedenle İYE'nin erkenden tanısını koyabilecek biyomarkerlara ihtiyaç bulunmaktadır. Bu çalışmada amacımız galektin-3'ün bu amaçla kullanılıp kullanılamayacağını test etmektir.Gereç ve Yöntem: Abant İzzet Baysal Üniversitesi Etik kurulu tarafından onaylanan ve üniversitesi BAP kurulunca desteklenen bu çalışma, Eylül 2015 - Eylül 2016 tarihleri arasında yapıldı. Hedef kitlemiz 1 ay-18 yaş aralığındaki hastalardı. Çalışmaya, idrar kültürü sonucuna göre İYE tanısı konulan 30 hasta ve 30 sağlıklı kişi dahil edildi. Tanı anında tam idrar tetkiki, hemogram, CRP ve sedimentasyon çalışıldı. Eş zamanlı olarak galektin-3, NGAL, IL-6 tetkikleri için serum örnekleri toplandı. Gerek görülen hastalara renal USG, VSUG ve DMSA görüntülemeleri yapıldı.Bulgular:Araştırmaya dahil edilen hastaların 17 tanesi (%56.6) kız ve 13 tanesi (%43.3) erkek idi. Hastaların 8 tanesi (%26.6) üst İYE ve 22 tanesi de (%73.3) alt İYE idi. Kontrol grubuna göre hasta grubunda serum galektin-3 (147.5±62.1 pg/ml'e karşılık 111.3±56.8 pg/ml, p=0.022), serum NGAL (131.9±71.3 ng/ml'e karşılık 97.2±50.3 ng/ml, p=0.03), WBC (9905±3464.4 µL'e karşılık 7037.6 ±1807.5 µL, p<0.001), nötrofil (5618.7± 3971.9 µL'e karşılık 3726.0±1443.9 µL, p=0.01), lenfosit (3269.3± 1786.8 µL'e karşılık 2359.7±1083.4 µL p=0.02) ve sedimentasyon (17±13 mm/saate karşılık 8.3±3.9 mm/saat, p=0.03) değerleri anlamlı oranda yüksekti.Ateş (%75'e karşılık %9, p=0.005) ve kostovertebral açıda hassasiyet (%100'e karşılık %0, p=0.003) üst İYE tanılı olanlarda anlamlı oranda yüksekti.Üst İYE tanılı olanlarda galektin-3 (185.3±60.7 pg/ml'ye karşılık 133.9±58 pg/ml, p=0.02), IL-6 (145.1±59 ng/L'a karşılık 84.8±64 ng/L, p=0.01), NGAL (171.9±77.3 ng/ml'a karşılık 117.4±64.8 ng/ml, p=0.05), nötrofil (9865.0±4653.3 µL'a karşılık 4074.5±2280.6 µL, p=0.001), CRP (95.8±58.8 mg/L'a karşılık 3.7±8.8 mg/L, p=0.001), eritrosit sedimentasyon hızı (32.9±15.5 mm/saate karşılık 11.3±6.0 mm/saat, p<0.001), NLR (6.0±3.2'a karşılık 1.5±1.6, p=0.02) ve CRP/MPV (14.0±8.6'a karşılık 0.5±1.2, p<0.001) değerleri anlamlı oranda yüksek idi.Serum galektin-3 seviyesi ile IL-6 (r=0.57, p=0.001), NGAL (r=0.68, p=0.001), CRP (r=0.4, p=0.02), sedimentasyon (r=0.38, p=0.03) ve CRP/MPV oranı (r=0.41, p=0.02) arasında anlamlı ve pozitif yönlü bir ilişki bulundu. Regresyon analizinde serum galektin-3 pozitifliğine ateşin (OR:7.7 (95% CI:1.1-52.1), p=0.04) ve kusmanın (OR:48.1, (95% CI:1.8-1235.4), p=0.02) etkisinin yanında CRP'nin (r²=0.14, p=0.01), sedimentasyonun (r²=0.18, p<0.001), IL-6'nın (r²=0.5, p<0.001) ve NGAL'in (r²=0.88, p<0.001) etkisinin olduğunu saptadık. İdrar kültürlerinde gram (-) üremesi olanlarda galektin-3 seviyesi 161.5±61.4 pg/ml iken, gram (+) olanlarda 99.5±22.3 pg/ml olarak saptandı (p=0.057).Üst İYE tanılı olanlardan 2 tanesinde (%40) renal skar saptandı. Galektin-3 düzeyi skar saptananlarda 217.7±30.9 pg/ml iken, saptanmayanlarda 122.9±38.2 pg/ml idi (p=0.054). Serum galektin-3'ün 94.8 pg/ml cut-off değerinde anlamlıya yakın oranda İYE tanısını (Sensitivite %57, spesifite %59, p=0.053) ve 130 pg/ml cut-off değerinde ise üst İYE tanısını koyabileceğini saptadık (Sensitivite %87, spesifite %68, p=0.02). Sonuç:Çalışmamızda denediğimiz serum galektin-3'ün hem İYE tanısını koymada ve hem de üst-alt İYE ayırımında geleneksel inflamasyon markerlarına alternatif olabileceğini düşünmekteyiz. Galektin-3'ün üst İYE bulguları olan ateş ve kusma yanında CRP, sedimentasyon, IL-6 ve NGAL gibi markerlar ile pozitif korelasyon göstermesi üst İYE tanısında kullanılabileceğine dair düşüncemizi güçlendirmiştir. Serum galektin-3'ün 94.8 pg/ml cut-off değerinde anlamlıya yakın oranda İYE tanısını koyabileceğini ve 130 pg/ml cut-off değerinde ise üst İYE'yi alt İYE'den ayırabileceğini saptadık Serum galektin-3 seviyesinin aynı zamanda İYE'de etken mikroorganizmanın grubuna ve renal skarın varlığına karar verilebilmesine de imkan verecek kadar istatiksel olarak anlamlıya yakın oranlarda artabilmektedir.

Seher Açar, M.D. The importance of galectin-3 used in the diagnoses of upper and lower urinary tract infections in pediatric patients, AİBÜ Faculty of Medicine, Department of Pediatrics, Thesis of Specialization in Medicine, Bolu, 2017Introduction: Urinary tract infections (UTI) are among the most common bacterial complaints, and are critical due to their acute effects as well as the problems they cause in the late term. The diverse range of clinical pictures among patients may delay diagnosis and treatment, pointing to the need for quick and reliable biomarkers that may provide early diagnosis and supply information on the severity and localization of UTI. This study aims to test whether a new biomarker, serum galectin-3, can be used for this purpose. Materials and Methods: Approved by the Ethics Committee of Abant İzzet Baysal University and supported by the Council of Scientific Research Projects, this study was carried out in the Pediatrics Clinic of the Training and Research Hospital of Abant İzzet Baysal University Faculty of Medicine between September 2015 and September 2016. The target group was comprised of patients aged between 1 month and 18 years who applied to our clinic. The study sample included 30 patients diagnosed with UTI according to 105 colony forming units in the urine culture, and 30 healthy individuals. Active complaints of patients at the time of diagnosis were noted down. Patients with growth of urinary culture were administered complete urine test, hemogram, CRP, and urine sediment at the time of diagnosis. Serum samples for galectin-3, NGAL, IL-6 tests were simultaneously taken. Renal USG, VSUG, and DMSA imaging was performed where necessary.Results: The study group was composed of 17 girls (56.6%) and 13 boys (43.3%) with a mean age of 6.3 years. Of the patients in the study group, 8 (26.6%) were diagnosed with upper UTI, and 22 (73.3%) with lower UTI. The number of patients diagnosed with recurrent UTI was 13 (43.3%).The analysis of the laboratory findings of all the individuals participating in the study revealed that the patient group had significantly higher levels of serum galectin-3 (147.5±62.1 pg/ml vs. 111.3±56.8 pg/ml, p=0.022), serum NGAL 131.9±71.3 ng/ml vs. 97.2±50.3 ng/ml, p=0.03), WBC (9905±3464.4 µL vs. 7037.6 ±1807.5 µL, p<0.001), neutrocytes (5618.7± 3971.9 µL vs. 3726.0±1443.9 µL, p=0.01), lymphocytes (3269.3± 1786.8 µL vs. 2359.7±1083.4 µL p=0.02), and sedimentation (17±13 mm/hour vs. 8.3±3.9 mm/hour, p=0.03) compared to healthy individuals.The analysis of clinical features of patients showed that upper UTI patients had significantly more severe complaints of fever (75% vs. 9%, p=0.005) and costovertabral angle tenderness (100% vs. 0%, p=0.003) when compared to patients with lower UTI. Laboratory analyses revealed that patients with upper UTI had significantly higher levels of galectin-3 (185.3±60.7 pg/ml vs. 133.9±58 pg/ml, p=0.02), IL-6 (145.1±59 ng/L vs. 84.8±64 ng/L, p=0.01), NGAL (171.9±77.3 ng/ml vs. 117.4±64.8 ng/ml, p=0.05), neutrocytes (9865.0±4653.3 µL vs. 4074.5±2280.6 µL, p=0.001), CRP (95.8±58.8 mg/L vs. 3.7±8.8 mg/L, p=0.001), erythrocyte sedimentation rate (32.9±15.5 mm/hour vs. 11.3±6.0 mm/hour, p<0.001), NLR (6.0±3.2 vs. 1.5±1.6, p=0.02) and CRP/MPV (14.0±8.6 vs. 0.5±1.2, p<0.001), and significantly lower levels of lymphocytes (1955.0±799.1 µL vs. 3747.3±1816.2 µL, p=0.003) and GFR (145.4±14.3 mL/min/1.73 m2 vs. 166.9±23.1 mL/min/1.73 m2, p=0.03) than lower UTI patients.A significant positive correlation was found between the level of serum galectin-3 and IL-6 (r=0.57, p=0.001), NGAL (r=0.68, p=0.001), CRP (r=0.4, p=0.02), sedimentation (r=0.38, p=0.03) and CRP/MPV rate (r=0.41, p=0.02) in the patient group.Logistic regression analysis showed that fever (OR:7.7 (95% CI:1.1-52.1), p=0.04) and vomiting (OR:48.1, (95% CI:1.8-1235.4), p=0.02) result in positive serum galectin-3. In addition, according to the findings of linear regression analysis, CRP (r²=0.14, p=0.01), sedimentation (r²=0.18, p<0.001), IL-6 (r²=0.5, p<0.001) and NGAL (r²=0.88, p<0.001) affect serum galectin-3 levels.Microorganisms growing in urine culture were classified as gram (+) and gram (-), and the galectin-3 level was found to be 161.5±61.4 pg/ml and 99.5±22.3 pg/ml in patients with gram (-) and gram (+) growth, respectively, indicating a nearly significant difference between the two groups (p=0.057). The number of patients with upper UTI that were given a DMSA scan was 5 (62.5%), and renal scarring was found in 2 of them (40%). The galectin-3 level was found to be 217.7±30.9 pg/ml and 122.9±38.2 pg/ml in patients with and without renal scarring, respectively. The difference between these two groups was nearly significant (p=0.054).In order to make a predictive diagnosis of UTI based on galectine-3 levels, a ROC curve including all participants was plotted, and it was found that serum galectin-3 may nearly significantly indicate UTI at the cutoff value of 94.8 pg/ml (sensitivity 57%, specificity 59%, p=0.053). Another ROC curve was plotted based on patients diagnosed with UTI to predict the diagnostic value of serum galectin-3 in upper UTI, which showed that serum galectin-3 can be used for upper UTI diagnosis at the cutoff value of 130 pg/ml (sensitivity 87%, specificity 68%, p=0.02). Conclusions: The findings of this study lead to the conclusion that serum galectin-3 may be an alternative to conventional inflammation markers both in the diagnosis of UTI and in the discrimination between upper and lower UTI. The observation that galectin-3 levels were higher in cases with upper UTI symptoms of fever and vomiting, and that galectin-3 was positively correlated with valid markers of upper UTI such as CRP, sedimentation, IL-6, and NGAL support the prospect of galectin-3 being used in the diagnosis of upper UTI. It was found that serum galectin-3 can serve as a nearly significant marker for diagnosis of UTI at the cut off value of 94.8 pg/ml, and discriminate upper UTI from lower UTI at the cutoff value of 130 pg/ml. Levels of serum galectin-3 may increase as to (nearly significantly) indicate which group active microorganisms belong to and whether renal scarring is present. There is a need for large scale studies for more reliable findings.